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overflow: hidden; text-overflow: ellipsis; -webkit-line-clamp: 3; -webkit-box-orient: vertical; }</style><div class="col-xs-12 clearfix"><div class="u-floatLeft"><h1 class="PageHeader-title u-m0x u-fs30">Apoptosis</h1><div class="u-tcGrayDark">23,011 Followers</div><div class="u-tcGrayDark u-mt2x">Recent papers in <b>Apoptosis</b></div></div></div></div></div></div><div class="TabbedNavigation"><div class="container"><div class="row"><div class="col-xs-12 clearfix"><ul class="nav u-m0x u-p0x list-inline u-displayFlex"><li class="active"><a href="https://www.academia.edu/Documents/in/Apoptosis">Top Papers</a></li><li><a href="https://www.academia.edu/Documents/in/Apoptosis/MostCited">Most Cited Papers</a></li><li><a href="https://www.academia.edu/Documents/in/Apoptosis/MostDownloaded">Most Downloaded Papers</a></li><li><a href="https://www.academia.edu/Documents/in/Apoptosis/MostRecent">Newest Papers</a></li><li><a class="" href="https://www.academia.edu/People/Apoptosis">People</a></li></ul></div><style type="text/css">ul.nav{flex-direction:row}@media(max-width: 567px){ul.nav{flex-direction:column}.TabbedNavigation li{max-width:100%}.TabbedNavigation li.active{background-color:var(--background-grey, #dddde2)}.TabbedNavigation li.active:before,.TabbedNavigation li.active:after{display:none}}</style></div></div></div><div class="container"><div class="row"><div class="col-xs-12"><div class="u-displayFlex"><div class="u-flexGrow1"><div class="works"><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_11231053" data-work_id="11231053" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/11231053/CD5_provides_viability_signals_to_B_cells_from_a_subset_of_B_CLL_patients_by_a_mechanism_that_involves_PKC">CD5 provides viability signals to B cells from a subset of B-CLL patients by a mechanism that involves PKC</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">B-chronic lymphocytic leukaemia (B-CLL) is a heterogeneous disease characterized by an accumulation of B lymphocytes expressing CD5. To date, the biological significance of this molecule in B-CLL B cells remains to be elucidated. In this... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_11231053" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">B-chronic lymphocytic leukaemia (B-CLL) is a heterogeneous disease characterized by an accumulation of B lymphocytes expressing CD5. To date, the biological significance of this molecule in B-CLL B cells remains to be elucidated. In this study, we have analysed the functional consequences of the binding of an anti-CD5 antibody on B-CLL B cells. To this purpose, we have measured the percentage of viability of B-CLL B cells in the presence or in the absence of anti-CD5 antibodies and also examined some of the biochemical events downstream the CD5-signalling. We demonstrate that anti-CD5 induces phosphorylation of protein tyrosine kinases and protein kinase C (PKC), while no activation of Akt/PKB and MAPKs is detected. This signalling cascade results in viability in a group of patients in which we observe an increase of Mcl-1 levels, whereas the levels of bcl-2, bcl-xL and XIAP do not change. We also report that this pathway leads to IL-10 production, an immunoregulatory cytokine that might act as an autocrine growth factor for leukaemic B cells. Inhibition of PKC prevents the induction of Mcl-1 and IL-10, suggesting that the activation of PKC plays an important role in the CD5-mediated survival signals in B cells from a subset of B-CLL patients.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/11231053" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="8d5502a4ada360cd7bfd607a24bb14e8" rel="nofollow" data-download="{"attachment_id":46805109,"asset_id":11231053,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/46805109/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="27139427" href="https://independent.academia.edu/PalomaPerezAciego">Paloma Perez-Aciego</a><script data-card-contents-for-user="27139427" type="text/json">{"id":27139427,"first_name":"Paloma","last_name":"Perez-Aciego","domain_name":"independent","page_name":"PalomaPerezAciego","display_name":"Paloma Perez-Aciego","profile_url":"https://independent.academia.edu/PalomaPerezAciego?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_11231053 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="11231053"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 11231053, container: ".js-paper-rank-work_11231053", }); 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$(".js-view-count[data-work-id=11231053]").text(description); $(".js-view-count-work_11231053").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_11231053").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="11231053"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">9</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="14109" rel="nofollow" href="https://www.academia.edu/Documents/in/Leukemia">Leukemia</a>, <script data-card-contents-for-ri="14109" type="text/json">{"id":14109,"name":"Leukemia","url":"https://www.academia.edu/Documents/in/Leukemia?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="38831" rel="nofollow" href="https://www.academia.edu/Documents/in/Signal_Transduction">Signal Transduction</a>, <script data-card-contents-for-ri="38831" type="text/json">{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="140106" rel="nofollow" href="https://www.academia.edu/Documents/in/Protein_Tyrosine_Kinase">Protein Tyrosine Kinase</a><script data-card-contents-for-ri="140106" type="text/json">{"id":140106,"name":"Protein Tyrosine Kinase","url":"https://www.academia.edu/Documents/in/Protein_Tyrosine_Kinase?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=11231053]'), work: {"id":11231053,"title":"CD5 provides viability signals to B cells from a subset of B-CLL patients by a mechanism that involves PKC","created_at":"2015-03-03T07:42:01.145-08:00","url":"https://www.academia.edu/11231053/CD5_provides_viability_signals_to_B_cells_from_a_subset_of_B_CLL_patients_by_a_mechanism_that_involves_PKC?f_ri=24731","dom_id":"work_11231053","summary":"B-chronic lymphocytic leukaemia (B-CLL) is a heterogeneous disease characterized by an accumulation of B lymphocytes expressing CD5. To date, the biological significance of this molecule in B-CLL B cells remains to be elucidated. In this study, we have analysed the functional consequences of the binding of an anti-CD5 antibody on B-CLL B cells. To this purpose, we have measured the percentage of viability of B-CLL B cells in the presence or in the absence of anti-CD5 antibodies and also examined some of the biochemical events downstream the CD5-signalling. We demonstrate that anti-CD5 induces phosphorylation of protein tyrosine kinases and protein kinase C (PKC), while no activation of Akt/PKB and MAPKs is detected. This signalling cascade results in viability in a group of patients in which we observe an increase of Mcl-1 levels, whereas the levels of bcl-2, bcl-xL and XIAP do not change. We also report that this pathway leads to IL-10 production, an immunoregulatory cytokine that might act as an autocrine growth factor for leukaemic B cells. Inhibition of PKC prevents the induction of Mcl-1 and IL-10, suggesting that the activation of PKC plays an important role in the CD5-mediated survival signals in B cells from a subset of B-CLL patients.","downloadable_attachments":[{"id":46805109,"asset_id":11231053,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":27139427,"first_name":"Paloma","last_name":"Perez-Aciego","domain_name":"independent","page_name":"PalomaPerezAciego","display_name":"Paloma Perez-Aciego","profile_url":"https://independent.academia.edu/PalomaPerezAciego?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":14109,"name":"Leukemia","url":"https://www.academia.edu/Documents/in/Leukemia?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true},{"id":140106,"name":"Protein Tyrosine Kinase","url":"https://www.academia.edu/Documents/in/Protein_Tyrosine_Kinase?f_ri=24731","nofollow":true},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731"},{"id":678853,"name":"B Lymphocytes","url":"https://www.academia.edu/Documents/in/B_Lymphocytes?f_ri=24731"},{"id":951344,"name":"Growth Factor","url":"https://www.academia.edu/Documents/in/Growth_Factor?f_ri=24731"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival?f_ri=24731"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_26521041" data-work_id="26521041" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/26521041/Targeted_shRNA_screening_identified_critical_roles_of_pleckstrin_2_in_erythropoiesis">Targeted shRNA screening identified critical roles of pleckstrin-2 in erythropoiesis</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest">Asterisks indicate genes that play dual functions in the early and late stages of terminal erythropoiesis.</div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/26521041" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="3c1be9f014579c4bd90d0341b46e8461" rel="nofollow" data-download="{"attachment_id":46817404,"asset_id":26521041,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/46817404/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="17117477" href="https://columbia.academia.edu/PengJi">Peng Ji</a><script data-card-contents-for-user="17117477" type="text/json">{"id":17117477,"first_name":"Peng","last_name":"Ji","domain_name":"columbia","page_name":"PengJi","display_name":"Peng Ji","profile_url":"https://columbia.academia.edu/PengJi?f_ri=24731","photo":"https://0.academia-photos.com/17117477/4709240/5432975/s65_peng.ji.jpg"}</script></span></span></li><li class="js-paper-rank-work_26521041 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="26521041"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 26521041, container: ".js-paper-rank-work_26521041", }); });</script></li><li class="js-percentile-work_26521041 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x 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$(".js-view-count-work_26521041").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_26521041").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="26521041"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">10</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="11298" rel="nofollow" href="https://www.academia.edu/Documents/in/Membrane_Proteins">Membrane Proteins</a>, <script data-card-contents-for-ri="11298" type="text/json">{"id":11298,"name":"Membrane Proteins","url":"https://www.academia.edu/Documents/in/Membrane_Proteins?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="15719" rel="nofollow" href="https://www.academia.edu/Documents/in/Mitochondria">Mitochondria</a>, <script data-card-contents-for-ri="15719" type="text/json">{"id":15719,"name":"Mitochondria","url":"https://www.academia.edu/Documents/in/Mitochondria?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="51121" rel="nofollow" href="https://www.academia.edu/Documents/in/RNA_interference">RNA interference</a><script data-card-contents-for-ri="51121" type="text/json">{"id":51121,"name":"RNA interference","url":"https://www.academia.edu/Documents/in/RNA_interference?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=26521041]'), work: {"id":26521041,"title":"Targeted shRNA screening identified critical roles of pleckstrin-2 in erythropoiesis","created_at":"2016-06-26T19:56:14.516-07:00","url":"https://www.academia.edu/26521041/Targeted_shRNA_screening_identified_critical_roles_of_pleckstrin_2_in_erythropoiesis?f_ri=24731","dom_id":"work_26521041","summary":"Asterisks indicate genes that play dual functions in the early and late stages of terminal erythropoiesis.","downloadable_attachments":[{"id":46817404,"asset_id":26521041,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":17117477,"first_name":"Peng","last_name":"Ji","domain_name":"columbia","page_name":"PengJi","display_name":"Peng Ji","profile_url":"https://columbia.academia.edu/PengJi?f_ri=24731","photo":"https://0.academia-photos.com/17117477/4709240/5432975/s65_peng.ji.jpg"}],"research_interests":[{"id":11298,"name":"Membrane Proteins","url":"https://www.academia.edu/Documents/in/Membrane_Proteins?f_ri=24731","nofollow":true},{"id":15719,"name":"Mitochondria","url":"https://www.academia.edu/Documents/in/Mitochondria?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":51121,"name":"RNA interference","url":"https://www.academia.edu/Documents/in/RNA_interference?f_ri=24731","nofollow":true},{"id":60436,"name":"Cell Differentiation","url":"https://www.academia.edu/Documents/in/Cell_Differentiation?f_ri=24731"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":409460,"name":"Erythropoiesis","url":"https://www.academia.edu/Documents/in/Erythropoiesis?f_ri=24731"},{"id":1010725,"name":"Protein Binding","url":"https://www.academia.edu/Documents/in/Protein_Binding?f_ri=24731"},{"id":1763968,"name":"Gene Expression Regulation","url":"https://www.academia.edu/Documents/in/Gene_Expression_Regulation?f_ri=24731"},{"id":1810445,"name":"Gene expression profiling","url":"https://www.academia.edu/Documents/in/Gene_expression_profiling?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_35426247" data-work_id="35426247" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/35426247/ADAMTS9_is_a_functional_tumor_suppressor_through_inhibiting_AKT_mTOR_pathway_and_associated_with_poor_survival_in_gastric_cancer">ADAMTS9 is a functional tumor suppressor through inhibiting AKT/mTOR pathway and associated with poor survival in gastric cancer</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Using genome-wide promoter methylation analysis, we identified a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9 (ADAMTS9) is methylated in cancer. We aim to clarify its epigenetic inactivation, biological function... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_35426247" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Using genome-wide promoter methylation analysis, we identified a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9 (ADAMTS9) is methylated in cancer. We aim to clarify its epigenetic inactivation, biological function and clinical implication in gastric cancer. ADAMTS9 was silenced in 6 out of 8 gastric cancer cell lines. The loss of ADAMTS9 expression was regulated by promoter hypermethylation and could be restored by demethylation agent. Ectopic expression of ADAMTS9 in gastric cancer cell lines (AGS, BGC823) inhibited cell growth curve in both the cell lines (Po0.0001), suppressed colony formation (Po0.01) and induced apoptosis (Po0.001 in AGS, Po0.01 in BGC823). Moreover, conditioned culture medium from ADAMTS9-transfected cell lines significantly disrupted the human umbilical vein endothelial cell tube formation capacity on Matrigel (Po0.01 in AGS, Po0.001 in BGC823). The in vivo growth of ADAMTS9 cells in nude mice was also markedly diminished after stable expression of ADAMTS9 (Po0.001). On the other hand, ADAMTS9 knockdown promoted cell proliferation (Po0.001). We further revealed that ADAMTS9 inhibited tumor growth by blocking activation of Akt and its downstream target the mammalian target of rapamycin (mTOR). ADAMTS9 also reduced phosphorylation of mTOR downstream targets p70 ribosomal S6 kinase, eIF4E-binding protein and downregulated hypoxia-inducible factor-1a. Therefore, this is the first demonstration that ADAMTS9 is a critical tumor suppressor of gastric cancer progression at least in part through suppression of oncogenic AKT/mTOR signaling. Moreover, promoter methylation of ADAMTS9 was detected in 29.2% (21/72) of primary gastric tumors. Multivariate analysis showed that patients with ADAMTS9 methylation had a poorer overall survival (relative risk (RR) ¼ 2.788; 95% confidence interval, 1.474-5.274; P ¼ 0.002). Kaplan-Meier survival curves showed that ADAMTS9 methylation was significantly associated with shortened survival in gastric cancer patients (P ¼ 0.001, log-rank test). In conclusion, ADAMTS9 acts as a functional tumor suppressor in gastric cancer through inhibiting oncogenic AKT/mTOR signaling pathway. Methylation of ADAMTS9 is an independent prognostic factor of gastric cancer.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/35426247" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="3d8530af7ad6012d58b88687801e9605" rel="nofollow" data-download="{"attachment_id":55287301,"asset_id":35426247,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/55287301/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="34296924" href="https://independent.academia.edu/XiaoxingLi">Xiaoxing Li</a><script data-card-contents-for-user="34296924" type="text/json">{"id":34296924,"first_name":"Xiaoxing","last_name":"Li","domain_name":"independent","page_name":"XiaoxingLi","display_name":"Xiaoxing Li","profile_url":"https://independent.academia.edu/XiaoxingLi?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_35426247 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="35426247"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 35426247, container: ".js-paper-rank-work_35426247", }); });</script></li><li class="js-percentile-work_35426247 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 35426247; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_35426247"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_35426247 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="35426247"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 35426247; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=35426247]").text(description); $(".js-view-count-work_35426247").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_35426247").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="35426247"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">8</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="10610" rel="nofollow" href="https://www.academia.edu/Documents/in/Survival_Analysis">Survival Analysis</a>, <script data-card-contents-for-ri="10610" type="text/json">{"id":10610,"name":"Survival Analysis","url":"https://www.academia.edu/Documents/in/Survival_Analysis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="38831" rel="nofollow" href="https://www.academia.edu/Documents/in/Signal_Transduction">Signal Transduction</a>, <script data-card-contents-for-ri="38831" type="text/json">{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="84760" rel="nofollow" href="https://www.academia.edu/Documents/in/Mice">Mice</a><script data-card-contents-for-ri="84760" type="text/json">{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=35426247]'), work: {"id":35426247,"title":"ADAMTS9 is a functional tumor suppressor through inhibiting AKT/mTOR pathway and associated with poor survival in gastric cancer","created_at":"2017-12-14T00:50:22.427-08:00","url":"https://www.academia.edu/35426247/ADAMTS9_is_a_functional_tumor_suppressor_through_inhibiting_AKT_mTOR_pathway_and_associated_with_poor_survival_in_gastric_cancer?f_ri=24731","dom_id":"work_35426247","summary":"Using genome-wide promoter methylation analysis, we identified a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9 (ADAMTS9) is methylated in cancer. We aim to clarify its epigenetic inactivation, biological function and clinical implication in gastric cancer. ADAMTS9 was silenced in 6 out of 8 gastric cancer cell lines. The loss of ADAMTS9 expression was regulated by promoter hypermethylation and could be restored by demethylation agent. Ectopic expression of ADAMTS9 in gastric cancer cell lines (AGS, BGC823) inhibited cell growth curve in both the cell lines (Po0.0001), suppressed colony formation (Po0.01) and induced apoptosis (Po0.001 in AGS, Po0.01 in BGC823). Moreover, conditioned culture medium from ADAMTS9-transfected cell lines significantly disrupted the human umbilical vein endothelial cell tube formation capacity on Matrigel (Po0.01 in AGS, Po0.001 in BGC823). The in vivo growth of ADAMTS9 cells in nude mice was also markedly diminished after stable expression of ADAMTS9 (Po0.001). On the other hand, ADAMTS9 knockdown promoted cell proliferation (Po0.001). We further revealed that ADAMTS9 inhibited tumor growth by blocking activation of Akt and its downstream target the mammalian target of rapamycin (mTOR). ADAMTS9 also reduced phosphorylation of mTOR downstream targets p70 ribosomal S6 kinase, eIF4E-binding protein and downregulated hypoxia-inducible factor-1a. Therefore, this is the first demonstration that ADAMTS9 is a critical tumor suppressor of gastric cancer progression at least in part through suppression of oncogenic AKT/mTOR signaling. Moreover, promoter methylation of ADAMTS9 was detected in 29.2% (21/72) of primary gastric tumors. Multivariate analysis showed that patients with ADAMTS9 methylation had a poorer overall survival (relative risk (RR) ¼ 2.788; 95% confidence interval, 1.474-5.274; P ¼ 0.002). Kaplan-Meier survival curves showed that ADAMTS9 methylation was significantly associated with shortened survival in gastric cancer patients (P ¼ 0.001, log-rank test). In conclusion, ADAMTS9 acts as a functional tumor suppressor in gastric cancer through inhibiting oncogenic AKT/mTOR signaling pathway. Methylation of ADAMTS9 is an independent prognostic factor of gastric cancer.","downloadable_attachments":[{"id":55287301,"asset_id":35426247,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":34296924,"first_name":"Xiaoxing","last_name":"Li","domain_name":"independent","page_name":"XiaoxingLi","display_name":"Xiaoxing Li","profile_url":"https://independent.academia.edu/XiaoxingLi?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":10610,"name":"Survival Analysis","url":"https://www.academia.edu/Documents/in/Survival_Analysis?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731","nofollow":true},{"id":106169,"name":"Oncogene","url":"https://www.academia.edu/Documents/in/Oncogene?f_ri=24731"},{"id":121665,"name":"DNA methylation","url":"https://www.academia.edu/Documents/in/DNA_methylation?f_ri=24731"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_32961611 coauthored" data-work_id="32961611" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/32961611/IL_33_activates_tumor_stroma_to_promote_intestinal_polyposis">IL-33 activates tumor stroma to promote intestinal polyposis</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_32961611" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the Apc Min/+ mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in Apc Min/+ polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in Apc Min/+ polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/32961611" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="4515a5c1517838188587cf6f08d07bb2" rel="nofollow" data-download="{"attachment_id":53087608,"asset_id":32961611,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/53087608/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="33124996" href="https://independent.academia.edu/NathanBerger2">Nathan Berger</a><script data-card-contents-for-user="33124996" type="text/json">{"id":33124996,"first_name":"Nathan","last_name":"Berger","domain_name":"independent","page_name":"NathanBerger2","display_name":"Nathan Berger","profile_url":"https://independent.academia.edu/NathanBerger2?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-32961611">+1</span><div class="hidden js-additional-users-32961611"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://independent.academia.edu/CarloSalvo">Carlo De Salvo</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-32961611'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-32961611').html(); } } new HoverPopover(popoverSettings); })();</script></li><li class="js-paper-rank-work_32961611 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="32961611"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 32961611, container: ".js-paper-rank-work_32961611", }); });</script></li><li class="js-percentile-work_32961611 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 32961611; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_32961611"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_32961611 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="32961611"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 32961611; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=32961611]").text(description); $(".js-view-count-work_32961611").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_32961611").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="32961611"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">13</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="8991" rel="nofollow" href="https://www.academia.edu/Documents/in/Wound_Healing">Wound Healing</a>, <script data-card-contents-for-ri="8991" type="text/json">{"id":8991,"name":"Wound Healing","url":"https://www.academia.edu/Documents/in/Wound_Healing?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="15570" rel="nofollow" href="https://www.academia.edu/Documents/in/Mast_Cells">Mast Cells</a>, <script data-card-contents-for-ri="15570" type="text/json">{"id":15570,"name":"Mast Cells","url":"https://www.academia.edu/Documents/in/Mast_Cells?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="28235" rel="nofollow" href="https://www.academia.edu/Documents/in/Multidisciplinary">Multidisciplinary</a><script data-card-contents-for-ri="28235" type="text/json">{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=32961611]'), work: {"id":32961611,"title":"IL-33 activates tumor stroma to promote intestinal polyposis","created_at":"2017-05-11T09:18:23.987-07:00","url":"https://www.academia.edu/32961611/IL_33_activates_tumor_stroma_to_promote_intestinal_polyposis?f_ri=24731","dom_id":"work_32961611","summary":"Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the Apc Min/+ mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in Apc Min/+ polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in Apc Min/+ polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment.","downloadable_attachments":[{"id":53087608,"asset_id":32961611,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":33124996,"first_name":"Nathan","last_name":"Berger","domain_name":"independent","page_name":"NathanBerger2","display_name":"Nathan Berger","profile_url":"https://independent.academia.edu/NathanBerger2?f_ri=24731","photo":"/images/s65_no_pic.png"},{"id":34875073,"first_name":"Carlo","last_name":"De Salvo","domain_name":"independent","page_name":"CarloSalvo","display_name":"Carlo De Salvo","profile_url":"https://independent.academia.edu/CarloSalvo?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":8991,"name":"Wound Healing","url":"https://www.academia.edu/Documents/in/Wound_Healing?f_ri=24731","nofollow":true},{"id":15570,"name":"Mast Cells","url":"https://www.academia.edu/Documents/in/Mast_Cells?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary?f_ri=24731","nofollow":true},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731"},{"id":43761,"name":"Transcriptome","url":"https://www.academia.edu/Documents/in/Transcriptome?f_ri=24731"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":239816,"name":"Myofibroblasts","url":"https://www.academia.edu/Documents/in/Myofibroblasts?f_ri=24731"},{"id":379416,"name":"Epithelial cells","url":"https://www.academia.edu/Documents/in/Epithelial_cells?f_ri=24731"},{"id":518062,"name":"Interleukins","url":"https://www.academia.edu/Documents/in/Interleukins?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"},{"id":1357909,"name":"Intestinal Polyposis","url":"https://www.academia.edu/Documents/in/Intestinal_Polyposis?f_ri=24731"},{"id":2440562,"name":"Colorectal Neoplasms","url":"https://www.academia.edu/Documents/in/Colorectal_Neoplasms?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_45077444" data-work_id="45077444" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/45077444/Castration_resistant_Prostate_Cancer_From_New_Pathophysiology_to_New_Treatment_Targets">Castration-resistant Prostate Cancer: From New Pathophysiology to New Treatment Targets</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest">ContextCastration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited.</div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/45077444" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="7a8324c3ecb3c8729d1c675aa34c4b2d" rel="nofollow" data-download="{"attachment_id":65635309,"asset_id":45077444,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/65635309/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="185020643" href="https://uclep.academia.edu/BertrandTOMBAL">Bertrand TOMBAL</a><script data-card-contents-for-user="185020643" type="text/json">{"id":185020643,"first_name":"Bertrand","last_name":"TOMBAL","domain_name":"uclep","page_name":"BertrandTOMBAL","display_name":"Bertrand TOMBAL","profile_url":"https://uclep.academia.edu/BertrandTOMBAL?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_45077444 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="45077444"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 45077444, container: ".js-paper-rank-work_45077444", }); 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$(".js-view-count[data-work-id=45077444]").text(description); $(".js-view-count-work_45077444").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_45077444").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="45077444"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">18</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="622" rel="nofollow" href="https://www.academia.edu/Documents/in/Nephrology">Nephrology</a>, <script data-card-contents-for-ri="622" type="text/json">{"id":622,"name":"Nephrology","url":"https://www.academia.edu/Documents/in/Nephrology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="6021" rel="nofollow" href="https://www.academia.edu/Documents/in/Cancer">Cancer</a>, <script data-card-contents-for-ri="6021" type="text/json">{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="12980" rel="nofollow" href="https://www.academia.edu/Documents/in/Prostate_Cancer">Prostate Cancer</a>, <script data-card-contents-for-ri="12980" type="text/json">{"id":12980,"name":"Prostate Cancer","url":"https://www.academia.edu/Documents/in/Prostate_Cancer?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a><script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=45077444]'), work: {"id":45077444,"title":"Castration-resistant Prostate Cancer: From New Pathophysiology to New Treatment Targets","created_at":"2021-02-08T04:37:59.880-08:00","url":"https://www.academia.edu/45077444/Castration_resistant_Prostate_Cancer_From_New_Pathophysiology_to_New_Treatment_Targets?f_ri=24731","dom_id":"work_45077444","summary":"ContextCastration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited.","downloadable_attachments":[{"id":65635309,"asset_id":45077444,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":185020643,"first_name":"Bertrand","last_name":"TOMBAL","domain_name":"uclep","page_name":"BertrandTOMBAL","display_name":"Bertrand TOMBAL","profile_url":"https://uclep.academia.edu/BertrandTOMBAL?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":622,"name":"Nephrology","url":"https://www.academia.edu/Documents/in/Nephrology?f_ri=24731","nofollow":true},{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer?f_ri=24731","nofollow":true},{"id":12980,"name":"Prostate Cancer","url":"https://www.academia.edu/Documents/in/Prostate_Cancer?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":39001,"name":"Pathophysiology","url":"https://www.academia.edu/Documents/in/Pathophysiology?f_ri=24731"},{"id":48981,"name":"Molecular chaperones","url":"https://www.academia.edu/Documents/in/Molecular_chaperones?f_ri=24731"},{"id":96098,"name":"Resistance","url":"https://www.academia.edu/Documents/in/Resistance?f_ri=24731"},{"id":112576,"name":"Cell Death","url":"https://www.academia.edu/Documents/in/Cell_Death?f_ri=24731"},{"id":126863,"name":"Immunotherapy","url":"https://www.academia.edu/Documents/in/Immunotherapy?f_ri=24731"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731"},{"id":288801,"name":"Apoptose","url":"https://www.academia.edu/Documents/in/Apoptose?f_ri=24731"},{"id":590252,"name":"Androgen Receptor","url":"https://www.academia.edu/Documents/in/Androgen_Receptor?f_ri=24731"},{"id":1639402,"name":"nuclear factor kappa B","url":"https://www.academia.edu/Documents/in/nuclear_factor_kappa_B?f_ri=24731"},{"id":1750086,"name":"Insulin Like Growth Factor","url":"https://www.academia.edu/Documents/in/Insulin_Like_Growth_Factor?f_ri=24731"},{"id":1810430,"name":"Chaperone","url":"https://www.academia.edu/Documents/in/Chaperone?f_ri=24731"},{"id":1953384,"name":"Activator","url":"https://www.academia.edu/Documents/in/Activator?f_ri=24731"},{"id":3205111,"name":"Prostatic neoplasms","url":"https://www.academia.edu/Documents/in/Prostatic_neoplasms?f_ri=24731"},{"id":3752792,"name":"orchiectomy","url":"https://www.academia.edu/Documents/in/orchiectomy?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_10530068" data-work_id="10530068" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/10530068/Regulation_of_autophagy_by_polyphenolic_compounds_as_a_potential_therapeutic_strategy_for_cancer">Regulation of autophagy by polyphenolic compounds as a potential therapeutic strategy for cancer</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Autophagy, a lysosomal degradation pathway for cellular constituents and organelles, is an adaptive and essential process required for cellular homeostasis. Although autophagy functions as a survival mechanism in response to cellular... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_10530068" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Autophagy, a lysosomal degradation pathway for cellular constituents and organelles, is an adaptive and essential process required for cellular homeostasis. Although autophagy functions as a survival mechanism in response to cellular stressors such as nutrient or growth factor deprivation, it can also lead to a non-apoptotic form of programmed cell death (PCD) called autophagyinduced cell death or autophagy-associated cell death (type II PCD). Current evidence suggests that cell death through autophagy can be induced as an alternative to apoptosis (type I PCD), with therapeutic purpose in cancer cells that are resistant to apoptosis. Thus, modulating autophagy is of great interest in cancer research and therapy. Natural polyphenolic compounds that are present in our diet, such as rottlerin, genistein, quercetin, curcumin, and resveratrol, can trigger type II PCD via various mechanisms through the canonical (Beclin-1 dependent) and non-canonical (Beclin-1 independent) routes of autophagy. The capacity of these compounds to provide a means of cancer cell death that enhances the effects of standard therapies should be taken into consideration for designing novel therapeutic strategies. This review focuses on the autophagy-and cell death-inducing effects of these polyphenolic compounds in cancer.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/10530068" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="1b705bd49c633452a4595e21921555ed" rel="nofollow" data-download="{"attachment_id":47322678,"asset_id":10530068,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/47322678/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="25805988" href="https://freakshare.academia.edu/nuraedahhasima">nuraedah hasima</a><script data-card-contents-for-user="25805988" type="text/json">{"id":25805988,"first_name":"nuraedah","last_name":"hasima","domain_name":"freakshare","page_name":"nuraedahhasima","display_name":"nuraedah hasima","profile_url":"https://freakshare.academia.edu/nuraedahhasima?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_10530068 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="10530068"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 10530068, container: ".js-paper-rank-work_10530068", }); });</script></li><li class="js-percentile-work_10530068 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 10530068; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_10530068"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_10530068 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="10530068"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 10530068; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=10530068]").text(description); $(".js-view-count-work_10530068").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_10530068").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="10530068"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">9</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="6021" rel="nofollow" href="https://www.academia.edu/Documents/in/Cancer">Cancer</a>, <script data-card-contents-for-ri="6021" type="text/json">{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="17923" rel="nofollow" href="https://www.academia.edu/Documents/in/Autophagy">Autophagy</a>, <script data-card-contents-for-ri="17923" type="text/json">{"id":17923,"name":"Autophagy","url":"https://www.academia.edu/Documents/in/Autophagy?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="23163" rel="nofollow" href="https://www.academia.edu/Documents/in/Stem_Cell">Stem Cell</a>, <script data-card-contents-for-ri="23163" type="text/json">{"id":23163,"name":"Stem Cell","url":"https://www.academia.edu/Documents/in/Stem_Cell?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a><script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=10530068]'), work: {"id":10530068,"title":"Regulation of autophagy by polyphenolic compounds as a potential therapeutic strategy for cancer","created_at":"2015-02-05T01:10:26.837-08:00","url":"https://www.academia.edu/10530068/Regulation_of_autophagy_by_polyphenolic_compounds_as_a_potential_therapeutic_strategy_for_cancer?f_ri=24731","dom_id":"work_10530068","summary":"Autophagy, a lysosomal degradation pathway for cellular constituents and organelles, is an adaptive and essential process required for cellular homeostasis. Although autophagy functions as a survival mechanism in response to cellular stressors such as nutrient or growth factor deprivation, it can also lead to a non-apoptotic form of programmed cell death (PCD) called autophagyinduced cell death or autophagy-associated cell death (type II PCD). Current evidence suggests that cell death through autophagy can be induced as an alternative to apoptosis (type I PCD), with therapeutic purpose in cancer cells that are resistant to apoptosis. Thus, modulating autophagy is of great interest in cancer research and therapy. Natural polyphenolic compounds that are present in our diet, such as rottlerin, genistein, quercetin, curcumin, and resveratrol, can trigger type II PCD via various mechanisms through the canonical (Beclin-1 dependent) and non-canonical (Beclin-1 independent) routes of autophagy. The capacity of these compounds to provide a means of cancer cell death that enhances the effects of standard therapies should be taken into consideration for designing novel therapeutic strategies. This review focuses on the autophagy-and cell death-inducing effects of these polyphenolic compounds in cancer.","downloadable_attachments":[{"id":47322678,"asset_id":10530068,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":25805988,"first_name":"nuraedah","last_name":"hasima","domain_name":"freakshare","page_name":"nuraedahhasima","display_name":"nuraedah hasima","profile_url":"https://freakshare.academia.edu/nuraedahhasima?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer?f_ri=24731","nofollow":true},{"id":17923,"name":"Autophagy","url":"https://www.academia.edu/Documents/in/Autophagy?f_ri=24731","nofollow":true},{"id":23163,"name":"Stem Cell","url":"https://www.academia.edu/Documents/in/Stem_Cell?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":42132,"name":"Transcription","url":"https://www.academia.edu/Documents/in/Transcription?f_ri=24731"},{"id":67405,"name":"Toxicity","url":"https://www.academia.edu/Documents/in/Toxicity?f_ri=24731"},{"id":112576,"name":"Cell Death","url":"https://www.academia.edu/Documents/in/Cell_Death?f_ri=24731"},{"id":495569,"name":"Signaling","url":"https://www.academia.edu/Documents/in/Signaling?f_ri=24731"},{"id":1954130,"name":"Cell Growth","url":"https://www.academia.edu/Documents/in/Cell_Growth?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_78704825" data-work_id="78704825" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/78704825/GABA_induces_the_differentiation_of_small_into_large_cholangiocytes_by_activation_of_Ca_2_CaMK_I_dependent_adenylyl_cyclase_8">GABA induces the differentiation of small into large cholangiocytes by activation of Ca 2+ /CaMK I-dependent adenylyl cyclase 8</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Large but not small cholangiocytes: (i) secrete bicarbonate by interaction with secretin receptors (SR) through activation of cystic fibrosis transmembrane regulator (CFTR), chloride bicarbonate anion exchanger 2 (Cl − /HCO 3 − AE2) and... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_78704825" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Large but not small cholangiocytes: (i) secrete bicarbonate by interaction with secretin receptors (SR) through activation of cystic fibrosis transmembrane regulator (CFTR), chloride bicarbonate anion exchanger 2 (Cl − /HCO 3 − AE2) and adenylyl cyclase 8 (AC8) (proteins regulating large biliary functions); and (ii) proliferate in response to bile duct ligation (BDL) by activation of cAMP signaling. Small, mitotically dormant cholangiocytes are activated during damage of large cholangiocytes by activation of IP 3 /Ca 2+-CaMK I. GABA affects cell functions by modulation of Ca 2+-dependent signaling and AC. We hypothesized that GABA induces the differentiation of small into large cholangiocytes by the activation of Ca 2+ /CaMK I-dependent AC 8. Methods-In vivo, BDL mice were treated with GABA in the absence/presence of BAPTA/AM or W7 before evaluating apoptosis and ductal mass (IBDM) of small and large cholangiocytes. In vitro, control-or CaMK I-silenced small cholangiocytes were treated with GABA for 3 days</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/78704825" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="4b6cb79ac3f3a50ac55ef79d99c9f95b" rel="nofollow" data-download="{"attachment_id":85658648,"asset_id":78704825,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/85658648/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="32865947" href="https://yamagata-u.academia.edu/YoshiyukiUeno">Yoshiyuki Ueno</a><script data-card-contents-for-user="32865947" type="text/json">{"id":32865947,"first_name":"Yoshiyuki","last_name":"Ueno","domain_name":"yamagata-u","page_name":"YoshiyukiUeno","display_name":"Yoshiyuki Ueno","profile_url":"https://yamagata-u.academia.edu/YoshiyukiUeno?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_78704825 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="78704825"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 78704825, container: ".js-paper-rank-work_78704825", }); 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$(".js-view-count[data-work-id=78704825]").text(description); $(".js-view-count-work_78704825").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_78704825").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="78704825"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">14</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="7710" rel="nofollow" href="https://www.academia.edu/Documents/in/Biology">Biology</a>, <script data-card-contents-for-ri="7710" type="text/json">{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="26327" rel="nofollow" href="https://www.academia.edu/Documents/in/Medicine">Medicine</a>, <script data-card-contents-for-ri="26327" type="text/json">{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="37773" rel="nofollow" href="https://www.academia.edu/Documents/in/Hepatology">Hepatology</a><script data-card-contents-for-ri="37773" type="text/json">{"id":37773,"name":"Hepatology","url":"https://www.academia.edu/Documents/in/Hepatology?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=78704825]'), work: {"id":78704825,"title":"GABA induces the differentiation of small into large cholangiocytes by activation of Ca 2+ /CaMK I-dependent adenylyl cyclase 8","created_at":"2022-05-07T15:06:36.824-07:00","url":"https://www.academia.edu/78704825/GABA_induces_the_differentiation_of_small_into_large_cholangiocytes_by_activation_of_Ca_2_CaMK_I_dependent_adenylyl_cyclase_8?f_ri=24731","dom_id":"work_78704825","summary":"Large but not small cholangiocytes: (i) secrete bicarbonate by interaction with secretin receptors (SR) through activation of cystic fibrosis transmembrane regulator (CFTR), chloride bicarbonate anion exchanger 2 (Cl − /HCO 3 − AE2) and adenylyl cyclase 8 (AC8) (proteins regulating large biliary functions); and (ii) proliferate in response to bile duct ligation (BDL) by activation of cAMP signaling. Small, mitotically dormant cholangiocytes are activated during damage of large cholangiocytes by activation of IP 3 /Ca 2+-CaMK I. GABA affects cell functions by modulation of Ca 2+-dependent signaling and AC. We hypothesized that GABA induces the differentiation of small into large cholangiocytes by the activation of Ca 2+ /CaMK I-dependent AC 8. Methods-In vivo, BDL mice were treated with GABA in the absence/presence of BAPTA/AM or W7 before evaluating apoptosis and ductal mass (IBDM) of small and large cholangiocytes. In vitro, control-or CaMK I-silenced small cholangiocytes were treated with GABA for 3 days","downloadable_attachments":[{"id":85658648,"asset_id":78704825,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":32865947,"first_name":"Yoshiyuki","last_name":"Ueno","domain_name":"yamagata-u","page_name":"YoshiyukiUeno","display_name":"Yoshiyuki Ueno","profile_url":"https://yamagata-u.academia.edu/YoshiyukiUeno?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine?f_ri=24731","nofollow":true},{"id":37773,"name":"Hepatology","url":"https://www.academia.edu/Documents/in/Hepatology?f_ri=24731","nofollow":true},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731"},{"id":60436,"name":"Cell Differentiation","url":"https://www.academia.edu/Documents/in/Cell_Differentiation?f_ri=24731"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":92680,"name":"cyclic AMP","url":"https://www.academia.edu/Documents/in/cyclic_AMP?f_ri=24731"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"},{"id":1619808,"name":"Gamma-Aminobutyric Acid","url":"https://www.academia.edu/Documents/in/Gamma-Aminobutyric_Acid?f_ri=24731"},{"id":3376795,"name":"Sulfonamides","url":"https://www.academia.edu/Documents/in/Sulfonamides?f_ri=24731"},{"id":3589281,"name":"Ligation","url":"https://www.academia.edu/Documents/in/Ligation?f_ri=24731"},{"id":3789880,"name":"Medical biochemistry and metabolomics","url":"https://www.academia.edu/Documents/in/Medical_biochemistry_and_metabolomics?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_72680151" data-work_id="72680151" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/72680151/Characterization_of_four_clones_derived_from_human_adenocarcinoma_cell_line_HT29_and_analysis_of_their_response_to_sodium_butyrate">Characterization of four clones derived from human adenocarcinoma cell line, HT29, and analysis of their response to sodium butyrate</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">The differentiation of colorectal cancer cells is associated with the arrest of tumor growth and tumor regression. However, the mechanism of such tumor cell differentiation has not yet been elucidated. Several adenocarcinoma cell lines,... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_72680151" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">The differentiation of colorectal cancer cells is associated with the arrest of tumor growth and tumor regression. However, the mechanism of such tumor cell differentiation has not yet been elucidated. Several adenocarcinoma cell lines, including HT29 which differentiates only upon stimulation with a differentiation agent, have been used for the study of colorectal cells. Since we had previously obtained variable results during analyses of these cells, we selected several clones of this cell line. In this study, four clones of the parental HT29 cells, H8, G9, G10 and A3, were characterized. All of them differentiated upon treatment with sodium butyrate as the differentiation agent but they appeared different in their response regarding some of the markers of differentiation. As revealed by ultrastructural analysis, H8 and G10 clones formed numerous intercellular cysts with microvilli whereas these structures were found only ocassionally in G9 and A3 clones. An elevated level of the indicator of cell differentiation, CEACAM 1, was found in H8 and G10 clones and the activity of alkaline phosphatase, another important marker of colorectal cell differentiation, was up-regulated and highly increased upon butyrate treatment in the H8 clone. Phosphorylation of p38 MAPK was increased in H8 and A3 butyrate-treated clones. According to the levels of cleaved PARP and activated caspase-3, the apoptotic response to butyrate appeared similar in all four clones, while electronoptic analysis revealed that clones G9 and A3 were more perceptive to butyrate-induced apoptosis. In conclusion, our data showed considerable heterogeneity in morphology and some enzymatic activity of the cloned cells. This fact may contribute to the evidence that many HT29 cells possess multipotent information similar to that of stem cells of the normal intestinal crypt.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/72680151" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="17d697c093c4daf66c9ea2d4b29f24ae" rel="nofollow" data-download="{"attachment_id":81512948,"asset_id":72680151,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/81512948/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="216193844" href="https://independent.academia.edu/MartinaVojtechova">Martina Vojtechova</a><script data-card-contents-for-user="216193844" type="text/json">{"id":216193844,"first_name":"Martina","last_name":"Vojtechova","domain_name":"independent","page_name":"MartinaVojtechova","display_name":"Martina Vojtechova","profile_url":"https://independent.academia.edu/MartinaVojtechova?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_72680151 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="72680151"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 72680151, container: ".js-paper-rank-work_72680151", }); 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$(".js-view-count[data-work-id=72680151]").text(description); $(".js-view-count-work_72680151").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_72680151").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="72680151"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">7</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="626" rel="nofollow" href="https://www.academia.edu/Documents/in/Oncology">Oncology</a>, <script data-card-contents-for-ri="626" type="text/json">{"id":626,"name":"Oncology","url":"https://www.academia.edu/Documents/in/Oncology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="60436" rel="nofollow" href="https://www.academia.edu/Documents/in/Cell_Differentiation">Cell Differentiation</a>, <script data-card-contents-for-ri="60436" type="text/json">{"id":60436,"name":"Cell Differentiation","url":"https://www.academia.edu/Documents/in/Cell_Differentiation?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="204435" rel="nofollow" href="https://www.academia.edu/Documents/in/Alkaline_phosphatase">Alkaline phosphatase</a><script data-card-contents-for-ri="204435" type="text/json">{"id":204435,"name":"Alkaline phosphatase","url":"https://www.academia.edu/Documents/in/Alkaline_phosphatase?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=72680151]'), work: {"id":72680151,"title":"Characterization of four clones derived from human adenocarcinoma cell line, HT29, and analysis of their response to sodium butyrate","created_at":"2022-03-01T05:55:12.299-08:00","url":"https://www.academia.edu/72680151/Characterization_of_four_clones_derived_from_human_adenocarcinoma_cell_line_HT29_and_analysis_of_their_response_to_sodium_butyrate?f_ri=24731","dom_id":"work_72680151","summary":"The differentiation of colorectal cancer cells is associated with the arrest of tumor growth and tumor regression. However, the mechanism of such tumor cell differentiation has not yet been elucidated. Several adenocarcinoma cell lines, including HT29 which differentiates only upon stimulation with a differentiation agent, have been used for the study of colorectal cells. Since we had previously obtained variable results during analyses of these cells, we selected several clones of this cell line. In this study, four clones of the parental HT29 cells, H8, G9, G10 and A3, were characterized. All of them differentiated upon treatment with sodium butyrate as the differentiation agent but they appeared different in their response regarding some of the markers of differentiation. As revealed by ultrastructural analysis, H8 and G10 clones formed numerous intercellular cysts with microvilli whereas these structures were found only ocassionally in G9 and A3 clones. An elevated level of the indicator of cell differentiation, CEACAM 1, was found in H8 and G10 clones and the activity of alkaline phosphatase, another important marker of colorectal cell differentiation, was up-regulated and highly increased upon butyrate treatment in the H8 clone. Phosphorylation of p38 MAPK was increased in H8 and A3 butyrate-treated clones. According to the levels of cleaved PARP and activated caspase-3, the apoptotic response to butyrate appeared similar in all four clones, while electronoptic analysis revealed that clones G9 and A3 were more perceptive to butyrate-induced apoptosis. In conclusion, our data showed considerable heterogeneity in morphology and some enzymatic activity of the cloned cells. This fact may contribute to the evidence that many HT29 cells possess multipotent information similar to that of stem cells of the normal intestinal crypt.","downloadable_attachments":[{"id":81512948,"asset_id":72680151,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":216193844,"first_name":"Martina","last_name":"Vojtechova","domain_name":"independent","page_name":"MartinaVojtechova","display_name":"Martina Vojtechova","profile_url":"https://independent.academia.edu/MartinaVojtechova?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":626,"name":"Oncology","url":"https://www.academia.edu/Documents/in/Oncology?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":60436,"name":"Cell Differentiation","url":"https://www.academia.edu/Documents/in/Cell_Differentiation?f_ri=24731","nofollow":true},{"id":204435,"name":"Alkaline phosphatase","url":"https://www.academia.edu/Documents/in/Alkaline_phosphatase?f_ri=24731","nofollow":true},{"id":1745478,"name":"Adenocarcinoma","url":"https://www.academia.edu/Documents/in/Adenocarcinoma?f_ri=24731"},{"id":1824499,"name":"Cell Adhesion Molecules","url":"https://www.academia.edu/Documents/in/Cell_Adhesion_Molecules?f_ri=24731"},{"id":2440562,"name":"Colorectal Neoplasms","url":"https://www.academia.edu/Documents/in/Colorectal_Neoplasms?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_63141830" data-work_id="63141830" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/63141830/B_cell_lymphoma_6_promotes_proliferation_and_survival_of_trophoblastic_cells">B-cell lymphoma 6 promotes proliferation and survival of trophoblastic cells</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Preeclampsia is one of the leading causes of maternal and perinatal mortality and morbidity and its pathogenesis is not fully understood. B-cell lymphoma 6 (BCL6), a key regulator of B-lymphocyte development, is altered in preeclamptic... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_63141830" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Preeclampsia is one of the leading causes of maternal and perinatal mortality and morbidity and its pathogenesis is not fully understood. B-cell lymphoma 6 (BCL6), a key regulator of B-lymphocyte development, is altered in preeclamptic placentas. We show here that BCL6 is present in all 3 studied trophoblast cell lines and it is predominantly expressed in trophoblastic HTR-8/SVneo cells derived from a 1 st trimester placenta, suggestive of its involvement in trophoblast expansion in the early stage of placental development. BCL6 is strongly stabilized upon stress stimulation. Inhibition of BCL6, by administrating either small interfering RNA or a specific small molecule inhibitor 79-6, reduces proliferation and induces apoptosis in trophoblastic cells. Intriguingly, depletion of BCL6 in HTR-8/SVneo cells results in a mitotic arrest associated with mitotic defects in centrosome integrity, indicative of its involvement in mitotic progression. Thus, like in haematopoietic cells and breast cancer cells, BCL6 promotes proliferation and facilitates survival of trophoblasts under stress situation. Further studies are required to decipher its molecular roles in differentiation, migration and the fusion process of trophoblasts. Whether increased BCL6 observed in preeclamptic placentas is one of the causes or the consequences of preeclampsia warrants further investigations in vivo and in vitro.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/63141830" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="2a493ceda7e61fa1741371f69b4515d7" rel="nofollow" data-download="{"attachment_id":75662020,"asset_id":63141830,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/75662020/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="33329488" href="https://uni-frankfurt.academia.edu/FrankLouwen">Frank Louwen</a><script data-card-contents-for-user="33329488" type="text/json">{"id":33329488,"first_name":"Frank","last_name":"Louwen","domain_name":"uni-frankfurt","page_name":"FrankLouwen","display_name":"Frank Louwen","profile_url":"https://uni-frankfurt.academia.edu/FrankLouwen?f_ri=24731","photo":"https://0.academia-photos.com/33329488/176842624/166902205/s65_frank.louwen.png"}</script></span></span></li><li class="js-paper-rank-work_63141830 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="63141830"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 63141830, container: ".js-paper-rank-work_63141830", }); 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$(".js-view-count[data-work-id=63141830]").text(description); $(".js-view-count-work_63141830").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_63141830").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="63141830"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">13</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="9113" rel="nofollow" href="https://www.academia.edu/Documents/in/Cell_Cycle">Cell Cycle</a>, <script data-card-contents-for-ri="9113" type="text/json">{"id":9113,"name":"Cell Cycle","url":"https://www.academia.edu/Documents/in/Cell_Cycle?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="38831" rel="nofollow" href="https://www.academia.edu/Documents/in/Signal_Transduction">Signal Transduction</a>, <script data-card-contents-for-ri="38831" type="text/json">{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="55267" rel="nofollow" href="https://www.academia.edu/Documents/in/Mitosis">Mitosis</a><script data-card-contents-for-ri="55267" type="text/json">{"id":55267,"name":"Mitosis","url":"https://www.academia.edu/Documents/in/Mitosis?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=63141830]'), work: {"id":63141830,"title":"B-cell lymphoma 6 promotes proliferation and survival of trophoblastic cells","created_at":"2021-12-03T10:43:33.819-08:00","url":"https://www.academia.edu/63141830/B_cell_lymphoma_6_promotes_proliferation_and_survival_of_trophoblastic_cells?f_ri=24731","dom_id":"work_63141830","summary":"Preeclampsia is one of the leading causes of maternal and perinatal mortality and morbidity and its pathogenesis is not fully understood. B-cell lymphoma 6 (BCL6), a key regulator of B-lymphocyte development, is altered in preeclamptic placentas. We show here that BCL6 is present in all 3 studied trophoblast cell lines and it is predominantly expressed in trophoblastic HTR-8/SVneo cells derived from a 1 st trimester placenta, suggestive of its involvement in trophoblast expansion in the early stage of placental development. BCL6 is strongly stabilized upon stress stimulation. Inhibition of BCL6, by administrating either small interfering RNA or a specific small molecule inhibitor 79-6, reduces proliferation and induces apoptosis in trophoblastic cells. Intriguingly, depletion of BCL6 in HTR-8/SVneo cells results in a mitotic arrest associated with mitotic defects in centrosome integrity, indicative of its involvement in mitotic progression. Thus, like in haematopoietic cells and breast cancer cells, BCL6 promotes proliferation and facilitates survival of trophoblasts under stress situation. Further studies are required to decipher its molecular roles in differentiation, migration and the fusion process of trophoblasts. Whether increased BCL6 observed in preeclamptic placentas is one of the causes or the consequences of preeclampsia warrants further investigations in vivo and in vitro.","downloadable_attachments":[{"id":75662020,"asset_id":63141830,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":33329488,"first_name":"Frank","last_name":"Louwen","domain_name":"uni-frankfurt","page_name":"FrankLouwen","display_name":"Frank Louwen","profile_url":"https://uni-frankfurt.academia.edu/FrankLouwen?f_ri=24731","photo":"https://0.academia-photos.com/33329488/176842624/166902205/s65_frank.louwen.png"}],"research_interests":[{"id":9113,"name":"Cell Cycle","url":"https://www.academia.edu/Documents/in/Cell_Cycle?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true},{"id":55267,"name":"Mitosis","url":"https://www.academia.edu/Documents/in/Mitosis?f_ri=24731","nofollow":true},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line?f_ri=24731"},{"id":62550,"name":"Pregnancy","url":"https://www.academia.edu/Documents/in/Pregnancy?f_ri=24731"},{"id":574882,"name":"Cell cycle checkpoints","url":"https://www.academia.edu/Documents/in/Cell_cycle_checkpoints?f_ri=24731"},{"id":678853,"name":"B Lymphocytes","url":"https://www.academia.edu/Documents/in/B_Lymphocytes?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival?f_ri=24731"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology?f_ri=24731"},{"id":1763968,"name":"Gene Expression Regulation","url":"https://www.academia.edu/Documents/in/Gene_Expression_Regulation?f_ri=24731"},{"id":1857822,"name":"Pre Eclampsia","url":"https://www.academia.edu/Documents/in/Pre_Eclampsia?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_50739920 coauthored" data-work_id="50739920" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/50739920/Nanocapsulated_curcumin_Oral_chemopreventive_formulation_against_diethylnitrosamine_induced_hepatocellular_carcinoma_in_rat">Nanocapsulated curcumin: Oral chemopreventive formulation against diethylnitrosamine induced hepatocellular carcinoma in rat</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Toxic outcome of chemical therapeutics as well as multidrug resistance are two serious phenomena for their inacceptance in cancer chemotherapy. Antioxidants like curcumin (Cur) have gained immense importance for their excellent... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_50739920" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Toxic outcome of chemical therapeutics as well as multidrug resistance are two serious phenomena for their inacceptance in cancer chemotherapy. Antioxidants like curcumin (Cur) have gained immense importance for their excellent anticarcinogenic activities and minimum toxic manifestations in biological system. However, Cur is lipophilic and thus following oral administration hardly appears in blood indicating its potential therapeutic challenge in cancer therapy. Nanocapsulated Cur has been used as a drug delivery vector to focus the effectiveness of these vesicles against hepatocellular carcinoma. The theme of work was to evaluate effectiveness in oral route of polylactide co-glycolide (PLGA) Nanocapsulated curcumin (Nano Cur) against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in rat. Nano Cur of average diameter 14 nm and encapsulation efficiency of 78% were prepared. Fourier Transform Infra Red (FTIR) analysis revealed that there is no chemical interaction between drug and the polymer. Three i.p. injections of the chemical hepatocarcinogen DEN at 15 days interval causes hepatotoxicity, the generation of reactive oxygen species (ROS), lipid peroxidation, decrease in plasma membrane microviscosity and depletion of antioxidant enzyme levels in liver. Nano Cur (weekly oral treatment for 16 weeks at 20 mg/kg b.wt) in DEN induced HCC rats exerted significant protection against HCC and restored redox homeostasis in liver cells. Nanocapsulated Cur caused cancer cell apoptosis as visualized by ApoBrdU analysis. Histopathological analysis confirmed the pathological improvement in the liver. Nano Cur was found to be a potential formulation in oral route in combating the oxidative damage of hepatic cells and eliminating DEN induced hepatocellular cancer cells in rat whereas identical amount of free Cur treatment was found almost ineffective.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/50739920" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="3bfec8de0b7eba0408a6bfde4215bdaa" rel="nofollow" data-download="{"attachment_id":68611484,"asset_id":50739920,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/68611484/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="105109995" href="https://independent.academia.edu/MandalArdhendu">Ardhendu Mandal</a><script data-card-contents-for-user="105109995" type="text/json">{"id":105109995,"first_name":"Ardhendu","last_name":"Mandal","domain_name":"independent","page_name":"MandalArdhendu","display_name":"Ardhendu Mandal","profile_url":"https://independent.academia.edu/MandalArdhendu?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-50739920">+1</span><div class="hidden js-additional-users-50739920"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://independent.academia.edu/KrishnaSaha26">Krishna Saha</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-50739920'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-50739920').html(); 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container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_50739920 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="50739920"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 50739920; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=50739920]").text(description); $(".js-view-count-work_50739920").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_50739920").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="50739920"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">18</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="24373" rel="nofollow" href="https://www.academia.edu/Documents/in/Atomic_Force_Microscopy">Atomic Force Microscopy</a>, <script data-card-contents-for-ri="24373" type="text/json">{"id":24373,"name":"Atomic Force Microscopy","url":"https://www.academia.edu/Documents/in/Atomic_Force_Microscopy?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="37834" rel="nofollow" href="https://www.academia.edu/Documents/in/Western_blotting">Western blotting</a>, <script data-card-contents-for-ri="37834" type="text/json">{"id":37834,"name":"Western blotting","url":"https://www.academia.edu/Documents/in/Western_blotting?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="54670" rel="nofollow" href="https://www.academia.edu/Documents/in/FTIR">FTIR</a><script data-card-contents-for-ri="54670" type="text/json">{"id":54670,"name":"FTIR","url":"https://www.academia.edu/Documents/in/FTIR?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=50739920]'), work: {"id":50739920,"title":"Nanocapsulated curcumin: Oral chemopreventive formulation against diethylnitrosamine induced hepatocellular carcinoma in rat","created_at":"2021-08-04T21:26:53.414-07:00","url":"https://www.academia.edu/50739920/Nanocapsulated_curcumin_Oral_chemopreventive_formulation_against_diethylnitrosamine_induced_hepatocellular_carcinoma_in_rat?f_ri=24731","dom_id":"work_50739920","summary":"Toxic outcome of chemical therapeutics as well as multidrug resistance are two serious phenomena for their inacceptance in cancer chemotherapy. Antioxidants like curcumin (Cur) have gained immense importance for their excellent anticarcinogenic activities and minimum toxic manifestations in biological system. However, Cur is lipophilic and thus following oral administration hardly appears in blood indicating its potential therapeutic challenge in cancer therapy. Nanocapsulated Cur has been used as a drug delivery vector to focus the effectiveness of these vesicles against hepatocellular carcinoma. The theme of work was to evaluate effectiveness in oral route of polylactide co-glycolide (PLGA) Nanocapsulated curcumin (Nano Cur) against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in rat. Nano Cur of average diameter 14 nm and encapsulation efficiency of 78% were prepared. Fourier Transform Infra Red (FTIR) analysis revealed that there is no chemical interaction between drug and the polymer. Three i.p. injections of the chemical hepatocarcinogen DEN at 15 days interval causes hepatotoxicity, the generation of reactive oxygen species (ROS), lipid peroxidation, decrease in plasma membrane microviscosity and depletion of antioxidant enzyme levels in liver. Nano Cur (weekly oral treatment for 16 weeks at 20 mg/kg b.wt) in DEN induced HCC rats exerted significant protection against HCC and restored redox homeostasis in liver cells. Nanocapsulated Cur caused cancer cell apoptosis as visualized by ApoBrdU analysis. Histopathological analysis confirmed the pathological improvement in the liver. Nano Cur was found to be a potential formulation in oral route in combating the oxidative damage of hepatic cells and eliminating DEN induced hepatocellular cancer cells in rat whereas identical amount of free Cur treatment was found almost ineffective.","downloadable_attachments":[{"id":68611484,"asset_id":50739920,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":105109995,"first_name":"Ardhendu","last_name":"Mandal","domain_name":"independent","page_name":"MandalArdhendu","display_name":"Ardhendu Mandal","profile_url":"https://independent.academia.edu/MandalArdhendu?f_ri=24731","photo":"/images/s65_no_pic.png"},{"id":213940580,"first_name":"Krishna","last_name":"Saha","domain_name":"independent","page_name":"KrishnaSaha26","display_name":"Krishna Saha","profile_url":"https://independent.academia.edu/KrishnaSaha26?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":24373,"name":"Atomic Force 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Data","url":"https://www.academia.edu/Documents/in/Molecular_Sequence_Data?f_ri=24731"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_45532296" data-work_id="45532296" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/45532296/Oncologic_trogocytosis_with_Hospicells_induces_the_expression_of_N_cadherin_by_breast_cancer_cells">Oncologic trogocytosis with Hospicells induces the expression of N-cadherin by breast cancer cells</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">In breast cancers, the appearance of metastasis is synonymous with poor prognosis. The metastatic process is usually associated with epithelial-mesenchymal transition (EMT) which is often induced by several soluble factors produced either... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_45532296" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">In breast cancers, the appearance of metastasis is synonymous with poor prognosis. The metastatic process is usually associated with epithelial-mesenchymal transition (EMT) which is often induced by several soluble factors produced either by the tumour cells themselves or by cells constituting the tumour microenvironment. The aim of the present study was to determine whether the mesenchymal properties given by some molecules such as N-cadherin, for instance, could be acquired by cancer cells via the trogocytosis process with cells of the tumour microenvironment. Hospicells are stromal cells which were first isolated from cancer cell aggregates of patients with ovarian cancer. We recently showed that these cells are immunosuppressive for T lymphocyte functions and confer chemoresistance to cancer cells by the transfer of the MDR protein via trogocytosis. In this study, we showed that a mammary cancer cell line (MDA-MB-231) acquires patches of membrane via oncologic trogocytosis with Hospicells. This unidirectional and active process depends on actin polymerization and can be increased via inhibition of the Src family and decreased via inhibition of PI3K. Trogocytosis between Hospicells and MDA-MB-231 does not lead to the direct acquisition of N-cadherin but rather it leads to the production of soluble factor(s) which induce de novo expression of N-cadherin by the cancer cells. The novelty here is that this factor is produced only if cancer cells interact and undergo trogocytosis with Hospicells. This new expression could confer a more invasive phenotype to the cancer cells and thus can explain the correlation of the presence of Hospicells with the number of invaded lymph nodes in patients with mammary adenocarcinoma.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/45532296" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="90cb4482d93ceaf7a2da2bcc350f8fc4" rel="nofollow" data-download="{"attachment_id":66015823,"asset_id":45532296,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/66015823/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="39140043" href="https://sorbonne-universites.academia.edu/ChristopheKlein">Christophe Klein</a><script data-card-contents-for-user="39140043" type="text/json">{"id":39140043,"first_name":"Christophe","last_name":"Klein","domain_name":"sorbonne-universites","page_name":"ChristopheKlein","display_name":"Christophe Klein","profile_url":"https://sorbonne-universites.academia.edu/ChristopheKlein?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_45532296 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="45532296"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 45532296, container: ".js-paper-rank-work_45532296", }); 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This new expression could confer a more invasive phenotype to the cancer cells and thus can explain the correlation of the presence of Hospicells with the number of invaded lymph nodes in patients with mammary adenocarcinoma.","downloadable_attachments":[{"id":66015823,"asset_id":45532296,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":39140043,"first_name":"Christophe","last_name":"Klein","domain_name":"sorbonne-universites","page_name":"ChristopheKlein","display_name":"Christophe Klein","profile_url":"https://sorbonne-universites.academia.edu/ChristopheKlein?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":626,"name":"Oncology","url":"https://www.academia.edu/Documents/in/Oncology?f_ri=24731","nofollow":true},{"id":5072,"name":"Molecular 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Cells","url":"https://www.academia.edu/Documents/in/Stromal_Cells?f_ri=24731"},{"id":811754,"name":"Cadherin","url":"https://www.academia.edu/Documents/in/Cadherin?f_ri=24731"},{"id":2528082,"name":"Cadherins","url":"https://www.academia.edu/Documents/in/Cadherins?f_ri=24731"},{"id":2847999,"name":"Breast Neoplasms","url":"https://www.academia.edu/Documents/in/Breast_Neoplasms?f_ri=24731"},{"id":3435849,"name":"coculture techniques","url":"https://www.academia.edu/Documents/in/coculture_techniques?f_ri=24731"},{"id":3681858,"name":"Trogocytosis","url":"https://www.academia.edu/Documents/in/Trogocytosis?f_ri=24731"},{"id":3881525,"name":"Ovarian Neoplasms","url":"https://www.academia.edu/Documents/in/Ovarian_Neoplasms?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_1813640" data-work_id="1813640" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/1813640/Phagocytosis_of_apoptotic_cells_in_mammals_caenorhabditis_elegans_and_Drosophila_melanogaster_molecular_mechanisms_and_physiological_consequences">Phagocytosis of apoptotic cells in mammals, caenorhabditis elegans and Drosophila melanogaster: molecular mechanisms and physiological consequences</a></div></div><div class="u-pb4x u-mt3x"></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/1813640" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li 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href="https://www.academia.edu/Documents/in/Drosophila_melanogaster">Drosophila melanogaster</a>, <script data-card-contents-for-ri="12768" type="text/json">{"id":12768,"name":"Drosophila melanogaster","url":"https://www.academia.edu/Documents/in/Drosophila_melanogaster?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="17491" rel="nofollow" href="https://www.academia.edu/Documents/in/Macrophages">Macrophages</a>, <script data-card-contents-for-ri="17491" type="text/json">{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a><script data-card-contents-for-ri="24731" 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Mechanics","url":"https://www.academia.edu/Documents/in/Molecular_Mechanics?f_ri=24731"},{"id":295260,"name":"Neutrophils","url":"https://www.academia.edu/Documents/in/Neutrophils?f_ri=24731"},{"id":376644,"name":"Phagocytosis","url":"https://www.academia.edu/Documents/in/Phagocytosis?f_ri=24731"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_29584137" data-work_id="29584137" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/29584137/Structure_and_sequence_variation_of_the_canine_perforin_gene">Structure and sequence variation of the canine perforin gene</a></div></div><div 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data-has-card-for-ri="173" rel="nofollow" href="https://www.academia.edu/Documents/in/Zoology">Zoology</a>, <script data-card-contents-for-ri="173" type="text/json">{"id":173,"name":"Zoology","url":"https://www.academia.edu/Documents/in/Zoology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="52438" rel="nofollow" href="https://www.academia.edu/Documents/in/Dogs">Dogs</a>, <script data-card-contents-for-ri="52438" type="text/json">{"id":52438,"name":"Dogs","url":"https://www.academia.edu/Documents/in/Dogs?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="54433" rel="nofollow" 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Bienzle","profile_url":"https://uoguelph.academia.edu/DorotheeBienzle?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":173,"name":"Zoology","url":"https://www.academia.edu/Documents/in/Zoology?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":52438,"name":"Dogs","url":"https://www.academia.edu/Documents/in/Dogs?f_ri=24731","nofollow":true},{"id":54433,"name":"Phylogeny","url":"https://www.academia.edu/Documents/in/Phylogeny?f_ri=24731","nofollow":true},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":121151,"name":"Histiocytic Sarcoma","url":"https://www.academia.edu/Documents/in/Histiocytic_Sarcoma?f_ri=24731"},{"id":224866,"name":"Gene Structure","url":"https://www.academia.edu/Documents/in/Gene_Structure?f_ri=24731"},{"id":283547,"name":"Introns","url":"https://www.academia.edu/Documents/in/Introns?f_ri=24731"},{"id":403740,"name":"Single Nucleotide Polymorphism","url":"https://www.academia.edu/Documents/in/Single_Nucleotide_Polymorphism?f_ri=24731"},{"id":420887,"name":"Viral Infection","url":"https://www.academia.edu/Documents/in/Viral_Infection?f_ri=24731"},{"id":555904,"name":"natural killer (NK) cell","url":"https://www.academia.edu/Documents/in/natural_killer_NK_cell?f_ri=24731"},{"id":644860,"name":"Veterinary Sciences","url":"https://www.academia.edu/Documents/in/Veterinary_Sciences?f_ri=24731"},{"id":782120,"name":"Veterinary Immunology","url":"https://www.academia.edu/Documents/in/Veterinary_Immunology?f_ri=24731"},{"id":784076,"name":"Species Specificity","url":"https://www.academia.edu/Documents/in/Species_Specificity?f_ri=24731"},{"id":809881,"name":"Amino Acid Sequence","url":"https://www.academia.edu/Documents/in/Amino_Acid_Sequence?f_ri=24731"},{"id":809882,"name":"Base Sequence","url":"https://www.academia.edu/Documents/in/Base_Sequence?f_ri=24731"},{"id":1327649,"name":"Perforin","url":"https://www.academia.edu/Documents/in/Perforin?f_ri=24731"},{"id":1409446,"name":"Granzyme","url":"https://www.academia.edu/Documents/in/Granzyme?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_6471580" data-work_id="6471580" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/6471580/Rapid_Upregulation_of_Caspase3_in_Rat_Spinal_Cord_after_Injury_mRNA_Protein_and_Cellular_Localization_Correlates_with_Apoptotic_Cell_Death">Rapid Upregulation of Caspase3 in Rat Spinal Cord after Injury: mRNA, Protein, and Cellular Localization Correlates with Apoptotic Cell Death</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Although the precise mechanisms explaining loss of, and failure to regain, function after spinal cord injury are unknown, there is increasing interest in the role of "secondary cell death." One prevalent theme in cell loss in other... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_6471580" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Although the precise mechanisms explaining loss of, and failure to regain, function after spinal cord injury are unknown, there is increasing interest in the role of "secondary cell death." One prevalent theme in cell loss in other regions of the CNS involves apoptosis executed by the intracellular caspase proteases. A recent study demonstrated that spinal cord injury rapidly increased the activation of caspase-3. Our previous studies demonstrated peak apoptosis in three of four cellular compartments 3 days after controlled contusion in the rat. We have extended these analyses to include enzyme and substrate studies of caspase subfamilies both in rostral and in caudal adjacent segments compared to the lesion site. Although presumed activation of programmed proenzyme is considered the mechanism for enhanced caspases, our novel analyses were designed to detect upregulation of gene expression. We surveyed traumatically injured spinal cord for caspase family messages with a modified differential mRNA display approach and found that the caspase-3 (CASP3) message was present and upregulated severalfold after injury. Our results clearly demonstrate that cell death in the spinal cord occurs after posttranslational activation of caspases that follow, at least for caspase-3, initial upregulation of CASP3 mRNA levels.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/6471580" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="98503b8561d5e8b299d79394cd58bc4a" rel="nofollow" data-download="{"attachment_id":48852159,"asset_id":6471580,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/48852159/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="10260110" href="https://kumc.academia.edu/BFestoff">Barry Festoff</a><script data-card-contents-for-user="10260110" type="text/json">{"id":10260110,"first_name":"Barry","last_name":"Festoff","domain_name":"kumc","page_name":"BFestoff","display_name":"Barry Festoff","profile_url":"https://kumc.academia.edu/BFestoff?f_ri=24731","photo":"https://0.academia-photos.com/10260110/18238724/18214156/s65_barry.festoff.jpg"}</script></span></span></li><li class="js-paper-rank-work_6471580 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="6471580"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 6471580, container: ".js-paper-rank-work_6471580", }); 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A recent study demonstrated that spinal cord injury rapidly increased the activation of caspase-3. Our previous studies demonstrated peak apoptosis in three of four cellular compartments 3 days after controlled contusion in the rat. We have extended these analyses to include enzyme and substrate studies of caspase subfamilies both in rostral and in caudal adjacent segments compared to the lesion site. Although presumed activation of programmed proenzyme is considered the mechanism for enhanced caspases, our novel analyses were designed to detect upregulation of gene expression. We surveyed traumatically injured spinal cord for caspase family messages with a modified differential mRNA display approach and found that the caspase-3 (CASP3) message was present and upregulated severalfold after injury. Our results clearly demonstrate that cell death in the spinal cord occurs after posttranslational activation of caspases that follow, at least for caspase-3, initial upregulation of CASP3 mRNA levels.","downloadable_attachments":[{"id":48852159,"asset_id":6471580,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":10260110,"first_name":"Barry","last_name":"Festoff","domain_name":"kumc","page_name":"BFestoff","display_name":"Barry Festoff","profile_url":"https://kumc.academia.edu/BFestoff?f_ri=24731","photo":"https://0.academia-photos.com/10260110/18238724/18214156/s65_barry.festoff.jpg"}],"research_interests":[{"id":221,"name":"Psychology","url":"https://www.academia.edu/Documents/in/Psychology?f_ri=24731","nofollow":true},{"id":11271,"name":"Motor neuron","url":"https://www.academia.edu/Documents/in/Motor_neuron?f_ri=24731","nofollow":true},{"id":22824,"name":"Spinal Cord Injury","url":"https://www.academia.edu/Documents/in/Spinal_Cord_Injury?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":27784,"name":"Gene expression","url":"https://www.academia.edu/Documents/in/Gene_expression?f_ri=24731"},{"id":37836,"name":"In Situ Hybridization","url":"https://www.academia.edu/Documents/in/In_Situ_Hybridization?f_ri=24731"},{"id":50841,"name":"Caspases","url":"https://www.academia.edu/Documents/in/Caspases?f_ri=24731"},{"id":99421,"name":"Spinal Cord","url":"https://www.academia.edu/Documents/in/Spinal_Cord?f_ri=24731"},{"id":100501,"name":"Microglia","url":"https://www.academia.edu/Documents/in/Microglia?f_ri=24731"},{"id":112576,"name":"Cell Death","url":"https://www.academia.edu/Documents/in/Cell_Death?f_ri=24731"},{"id":181569,"name":"Proteins","url":"https://www.academia.edu/Documents/in/Proteins?f_ri=24731"},{"id":201209,"name":"Biotin","url":"https://www.academia.edu/Documents/in/Biotin?f_ri=24731"},{"id":231661,"name":"Enzyme","url":"https://www.academia.edu/Documents/in/Enzyme?f_ri=24731"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731"},{"id":247477,"name":"Caspase","url":"https://www.academia.edu/Documents/in/Caspase?f_ri=24731"},{"id":329844,"name":"Experimental","url":"https://www.academia.edu/Documents/in/Experimental?f_ri=24731"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats?f_ri=24731"},{"id":432129,"name":"Substrate Specificity","url":"https://www.academia.edu/Documents/in/Substrate_Specificity?f_ri=24731"},{"id":664188,"name":"Experimental Neurology","url":"https://www.academia.edu/Documents/in/Experimental_Neurology?f_ri=24731"},{"id":964769,"name":"Differential Display","url":"https://www.academia.edu/Documents/in/Differential_Display?f_ri=24731"},{"id":1011135,"name":"Spinal Cord Injuries","url":"https://www.academia.edu/Documents/in/Spinal_Cord_Injuries?f_ri=24731"},{"id":1239755,"name":"Neurosciences","url":"https://www.academia.edu/Documents/in/Neurosciences?f_ri=24731"},{"id":1810445,"name":"Gene expression profiling","url":"https://www.academia.edu/Documents/in/Gene_expression_profiling?f_ri=24731"},{"id":2208075,"name":"Cysteine Proteinase Inhibitors","url":"https://www.academia.edu/Documents/in/Cysteine_Proteinase_Inhibitors?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_7826228" data-work_id="7826228" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/7826228/Methoxylated_isoflavones_cajanin_and_isoformononetin_have_non_estrogenic_bone_forming_effect_via_differential_mitogen_activated_protein_kinase_MAPK_signaling">Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Following a lead obtained from stem-bark extract of Butea monosperma, two structurally related methoxyisoflavones; cajanin and isoformononetin were studied for their effects in osteoblasts. Cajanin had strong mitogenic as well as... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_7826228" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Following a lead obtained from stem-bark extract of Butea monosperma, two structurally related methoxyisoflavones; cajanin and isoformononetin were studied for their effects in osteoblasts. Cajanin had strong mitogenic as well as differentiation-promoting effects on osteoblasts that involved subsequent activation of MEK-Erk and Akt pathways. On the other hand, isoformononetin exhibited potent anti-apoptotic effect in addition to promoting osteoblast differentiation that involved parallel activation of MEK-Erk and Akt pathways. Unlike genistein or daidzein, none of these two compounds appear to act via estrogen receptors in osteoblast. Once daily oral (by gavage) treatment for 30 consecutive days was given to recently weaned female Sprague–Dawley rats with each of these compounds at 10.0 mg kg−1 day−1 dose. Cajanin increased bone mineral density (BMD) at all skeletal sites studied, bone biomechanical strength, mineral apposition rate (MAR) and bone formation rate (BFR), compared with control. BMD levels at various anatomic positions were also increased with isoformononetin compared with control however, its effect was less potent than cajanin. Isoformononetin had no effect on the parameters of bone biomechanical strength although it enhanced MAR and BFR compared with control. Isoformononetin had very mild uterotrophic effect, whereas cajanin was devoid of any such effect. Our data suggest that cajanin is more potent than isoformononetin in accelerating peak bone mass achievement. To the best of our knowledge, this work represents the first attempt to elucidate structure-activity relationship between the two methoxylated isoflavones regarding their effects in osteoblasts and bone formation. J. Cell. Biochem. 108: 388–399, 2009. © 2009 Wiley-Liss, Inc.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/7826228" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="311b3cab021e9ab7f85037a72fc5f764" rel="nofollow" data-download="{"attachment_id":48325527,"asset_id":7826228,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/48325527/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="14530920" href="https://independent.academia.edu/divyasingh39">divya singh</a><script data-card-contents-for-user="14530920" type="text/json">{"id":14530920,"first_name":"divya","last_name":"singh","domain_name":"independent","page_name":"divyasingh39","display_name":"divya singh","profile_url":"https://independent.academia.edu/divyasingh39?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_7826228 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="7826228"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 7826228, container: ".js-paper-rank-work_7826228", }); 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cajanin and isoformononetin were studied for their effects in osteoblasts. Cajanin had strong mitogenic as well as differentiation-promoting effects on osteoblasts that involved subsequent activation of MEK-Erk and Akt pathways. On the other hand, isoformononetin exhibited potent anti-apoptotic effect in addition to promoting osteoblast differentiation that involved parallel activation of MEK-Erk and Akt pathways. Unlike genistein or daidzein, none of these two compounds appear to act via estrogen receptors in osteoblast. Once daily oral (by gavage) treatment for 30 consecutive days was given to recently weaned female Sprague–Dawley rats with each of these compounds at 10.0 mg kg−1 day−1 dose. Cajanin increased bone mineral density (BMD) at all skeletal sites studied, bone biomechanical strength, mineral apposition rate (MAR) and bone formation rate (BFR), compared with control. BMD levels at various anatomic positions were also increased with isoformononetin compared with control however, its effect was less potent than cajanin. Isoformononetin had no effect on the parameters of bone biomechanical strength although it enhanced MAR and BFR compared with control. Isoformononetin had very mild uterotrophic effect, whereas cajanin was devoid of any such effect. Our data suggest that cajanin is more potent than isoformononetin in accelerating peak bone mass achievement. To the best of our knowledge, this work represents the first attempt to elucidate structure-activity relationship between the two methoxylated isoflavones regarding their effects in osteoblasts and bone formation. J. Cell. Biochem. 108: 388–399, 2009. © 2009 Wiley-Liss, Inc.","downloadable_attachments":[{"id":48325527,"asset_id":7826228,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":14530920,"first_name":"divya","last_name":"singh","domain_name":"independent","page_name":"divyasingh39","display_name":"divya singh","profile_url":"https://independent.academia.edu/divyasingh39?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":6791,"name":"Aging","url":"https://www.academia.edu/Documents/in/Aging?f_ri=24731","nofollow":true},{"id":12981,"name":"Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Enzyme_Inhibitors?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":60436,"name":"Cell Differentiation","url":"https://www.academia.edu/Documents/in/Cell_Differentiation?f_ri=24731","nofollow":true},{"id":60915,"name":"Cellular","url":"https://www.academia.edu/Documents/in/Cellular?f_ri=24731"},{"id":139532,"name":"Bone Density","url":"https://www.academia.edu/Documents/in/Bone_Density?f_ri=24731"},{"id":213910,"name":"Mitogen Activated Protein Kinase","url":"https://www.academia.edu/Documents/in/Mitogen_Activated_Protein_Kinase?f_ri=24731"},{"id":358428,"name":"Estrogens","url":"https://www.academia.edu/Documents/in/Estrogens?f_ri=24731"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats?f_ri=24731"},{"id":413194,"name":"Analysis of Variance","url":"https://www.academia.edu/Documents/in/Analysis_of_Variance?f_ri=24731"},{"id":606066,"name":"Osteogenesis","url":"https://www.academia.edu/Documents/in/Osteogenesis?f_ri=24731"},{"id":667555,"name":"Genistein","url":"https://www.academia.edu/Documents/in/Genistein?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"},{"id":863330,"name":"Osteoblasts","url":"https://www.academia.edu/Documents/in/Osteoblasts?f_ri=24731"},{"id":987079,"name":"Uterus","url":"https://www.academia.edu/Documents/in/Uterus?f_ri=24731"},{"id":1229331,"name":"Phytoestrogens","url":"https://www.academia.edu/Documents/in/Phytoestrogens?f_ri=24731"},{"id":1256683,"name":"Bone and Bones","url":"https://www.academia.edu/Documents/in/Bone_and_Bones?f_ri=24731"},{"id":1296969,"name":"Molecular and Cellular Biochemistry","url":"https://www.academia.edu/Documents/in/Molecular_and_Cellular_Biochemistry?f_ri=24731"},{"id":1409896,"name":"Diethylstilbestrol","url":"https://www.academia.edu/Documents/in/Diethylstilbestrol?f_ri=24731"},{"id":1664707,"name":"Bone Marrow Cells","url":"https://www.academia.edu/Documents/in/Bone_Marrow_Cells?f_ri=24731"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_9395595" data-work_id="9395595" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/9395595/Lysosomal_enzymes_in_the_macronucleus_of_Tetrahymena_during_its_apoptosis_like_degradation">Lysosomal enzymes in the macronucleus of Tetrahymena during its apoptosis-like degradation</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">A key characteristic of apoptosis is its regulated nuclear degradation. Apoptosis-like nuclear degradation also occurs in the ciliated unicellular organism, Tetrahymena thermophila. Chromatin of the macronucleus undergoes massive... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_9395595" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">A key characteristic of apoptosis is its regulated nuclear degradation. Apoptosis-like nuclear degradation also occurs in the ciliated unicellular organism, Tetrahymena thermophila. Chromatin of the macronucleus undergoes massive condensation, a process that can be blocked by caspase inhibitors. The nucleus becomes TUNEL-positive, and its DNA is cleaved into nucleosome-sized fragments. In a matter of hours the macronucleus is completely degraded, and disappears. The condensed nucleus sequesters acridine orange, which means that it might become an acidic compartment. We therefore asked whether lysosomal bodies fuse with the condensed macronucleus to form an autophagosome. We monitored acid phosphatase (AP) activity, which is associated with lysosomal bodies but is not found in normal nuclei. We find that after the macronucleus condenses AP activity is localized in cap-like structures at its cortex. Later, after the degrading macronucleus loses much of its DNA, acid phosphatase deposits appear deeper within the nucleus. We conclude that although macronuclear elimination is initiated by an apoptosis-like mechanism, its final degradation may be achieved through autophagosomy. Cell Death and Differentiation (2001) 8, 289 ± 297.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/9395595" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="4ec8b3b036262fdc8fbc0c7060b37eeb" rel="nofollow" data-download="{"attachment_id":47799390,"asset_id":9395595,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/47799390/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="21815597" href="https://ucsd.academia.edu/EmilyLu">Emily Lu</a><script data-card-contents-for-user="21815597" type="text/json">{"id":21815597,"first_name":"Emily","last_name":"Lu","domain_name":"ucsd","page_name":"EmilyLu","display_name":"Emily Lu","profile_url":"https://ucsd.academia.edu/EmilyLu?f_ri=24731","photo":"https://0.academia-photos.com/21815597/5989942/6797294/s65_emily.lu.jpg_oh_abcd016ba4dd8b1cf09d155b265c2027_oe_54d73748___gda___1427307341_92ce8e92d98a672eb4be21f5b432c2ea"}</script></span></span></li><li class="js-paper-rank-work_9395595 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="9395595"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 9395595, container: ".js-paper-rank-work_9395595", }); 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Apoptosis-like nuclear degradation also occurs in the ciliated unicellular organism, Tetrahymena thermophila. Chromatin of the macronucleus undergoes massive condensation, a process that can be blocked by caspase inhibitors. The nucleus becomes TUNEL-positive, and its DNA is cleaved into nucleosome-sized fragments. In a matter of hours the macronucleus is completely degraded, and disappears. The condensed nucleus sequesters acridine orange, which means that it might become an acidic compartment. We therefore asked whether lysosomal bodies fuse with the condensed macronucleus to form an autophagosome. We monitored acid phosphatase (AP) activity, which is associated with lysosomal bodies but is not found in normal nuclei. We find that after the macronucleus condenses AP activity is localized in cap-like structures at its cortex. Later, after the degrading macronucleus loses much of its DNA, acid phosphatase deposits appear deeper within the nucleus. We conclude that although macronuclear elimination is initiated by an apoptosis-like mechanism, its final degradation may be achieved through autophagosomy. Cell Death and Differentiation (2001) 8, 289 ± 297.","downloadable_attachments":[{"id":47799390,"asset_id":9395595,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":21815597,"first_name":"Emily","last_name":"Lu","domain_name":"ucsd","page_name":"EmilyLu","display_name":"Emily Lu","profile_url":"https://ucsd.academia.edu/EmilyLu?f_ri=24731","photo":"https://0.academia-photos.com/21815597/5989942/6797294/s65_emily.lu.jpg_oh_abcd016ba4dd8b1cf09d155b265c2027_oe_54d73748___gda___1427307341_92ce8e92d98a672eb4be21f5b432c2ea"}],"research_interests":[{"id":4987,"name":"Kinetics","url":"https://www.academia.edu/Documents/in/Kinetics?f_ri=24731","nofollow":true},{"id":17923,"name":"Autophagy","url":"https://www.academia.edu/Documents/in/Autophagy?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences?f_ri=24731","nofollow":true},{"id":231661,"name":"Enzyme","url":"https://www.academia.edu/Documents/in/Enzyme?f_ri=24731"},{"id":238813,"name":"Chromatin","url":"https://www.academia.edu/Documents/in/Chromatin?f_ri=24731"},{"id":979298,"name":"Lysosomes","url":"https://www.academia.edu/Documents/in/Lysosomes?f_ri=24731"},{"id":1335153,"name":"Acridine Orange","url":"https://www.academia.edu/Documents/in/Acridine_Orange?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_9829916" data-work_id="9829916" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/9829916/Multiple_Cellular_Responses_to_Serotonin_Contribute_to_Epithelial_Homeostasis">Multiple Cellular Responses to Serotonin Contribute to Epithelial Homeostasis</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover) enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis) form... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_9829916" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover) enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis) form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A), we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis) to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers).</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/9829916" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="b16f5959ac9b23fcbab95d1e1e69d096" rel="nofollow" data-download="{"attachment_id":47634221,"asset_id":9829916,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/47634221/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="23715697" href="https://tufts.academia.edu/VaibhavPai">Vaibhav Pai</a><script data-card-contents-for-user="23715697" type="text/json">{"id":23715697,"first_name":"Vaibhav","last_name":"Pai","domain_name":"tufts","page_name":"VaibhavPai","display_name":"Vaibhav Pai","profile_url":"https://tufts.academia.edu/VaibhavPai?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_9829916 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="9829916"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 9829916, container: ".js-paper-rank-work_9829916", }); 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Epithelial cell differentiation and cell loss (cell shedding and apoptosis) form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A), we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis) to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers).","downloadable_attachments":[{"id":47634221,"asset_id":9829916,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":23715697,"first_name":"Vaibhav","last_name":"Pai","domain_name":"tufts","page_name":"VaibhavPai","display_name":"Vaibhav Pai","profile_url":"https://tufts.academia.edu/VaibhavPai?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":3471,"name":"Regeneration","url":"https://www.academia.edu/Documents/in/Regeneration?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary?f_ri=24731","nofollow":true},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true},{"id":51565,"name":"Serotonin","url":"https://www.academia.edu/Documents/in/Serotonin?f_ri=24731"},{"id":60436,"name":"Cell Differentiation","url":"https://www.academia.edu/Documents/in/Cell_Differentiation?f_ri=24731"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":220780,"name":"PLoS one","url":"https://www.academia.edu/Documents/in/PLoS_one?f_ri=24731"},{"id":379416,"name":"Epithelial cells","url":"https://www.academia.edu/Documents/in/Epithelial_cells?f_ri=24731"},{"id":379889,"name":"Homeostasis","url":"https://www.academia.edu/Documents/in/Homeostasis?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_13463698" data-work_id="13463698" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/13463698/Cytokine_Response_Modifier_A_CrmA_A_Strategically_Deployed_Viral_Weapon">Cytokine Response Modifier A (CrmA): A Strategically Deployed Viral Weapon</a></div></div><div class="u-pb4x u-mt3x"></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/13463698" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="f4aa892fcf8bbb7fd023a181b308e393" rel="nofollow" data-download="{"attachment_id":45318832,"asset_id":13463698,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/45318832/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="32690430" href="https://aub-lb.academia.edu/GhassanDbaibo">Ghassan Dbaibo</a><script data-card-contents-for-user="32690430" type="text/json">{"id":32690430,"first_name":"Ghassan","last_name":"Dbaibo","domain_name":"aub-lb","page_name":"GhassanDbaibo","display_name":"Ghassan Dbaibo","profile_url":"https://aub-lb.academia.edu/GhassanDbaibo?f_ri=24731","photo":"https://0.academia-photos.com/32690430/17936466/17949687/s65_ghassan.dbaibo.png"}</script></span></span></li><li class="js-paper-rank-work_13463698 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="13463698"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 13463698, container: ".js-paper-rank-work_13463698", }); });</script></li><li class="js-percentile-work_13463698 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 13463698; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_13463698"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_13463698 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="13463698"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 13463698; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=13463698]").text(description); $(".js-view-count-work_13463698").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_13463698").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="13463698"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">4</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="38831" rel="nofollow" href="https://www.academia.edu/Documents/in/Signal_Transduction">Signal Transduction</a>, <script data-card-contents-for-ri="38831" type="text/json">{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="1007684" rel="nofollow" href="https://www.academia.edu/Documents/in/Virus_diseases">Virus diseases</a>, <script data-card-contents-for-ri="1007684" type="text/json">{"id":1007684,"name":"Virus diseases","url":"https://www.academia.edu/Documents/in/Virus_diseases?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="2208075" rel="nofollow" href="https://www.academia.edu/Documents/in/Cysteine_Proteinase_Inhibitors">Cysteine Proteinase Inhibitors</a><script data-card-contents-for-ri="2208075" type="text/json">{"id":2208075,"name":"Cysteine Proteinase Inhibitors","url":"https://www.academia.edu/Documents/in/Cysteine_Proteinase_Inhibitors?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=13463698]'), work: {"id":13463698,"title":"Cytokine Response Modifier A (CrmA): A Strategically Deployed Viral Weapon","created_at":"2015-07-01T00:15:29.916-07:00","url":"https://www.academia.edu/13463698/Cytokine_Response_Modifier_A_CrmA_A_Strategically_Deployed_Viral_Weapon?f_ri=24731","dom_id":"work_13463698","summary":null,"downloadable_attachments":[{"id":45318832,"asset_id":13463698,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":32690430,"first_name":"Ghassan","last_name":"Dbaibo","domain_name":"aub-lb","page_name":"GhassanDbaibo","display_name":"Ghassan Dbaibo","profile_url":"https://aub-lb.academia.edu/GhassanDbaibo?f_ri=24731","photo":"https://0.academia-photos.com/32690430/17936466/17949687/s65_ghassan.dbaibo.png"}],"research_interests":[{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true},{"id":1007684,"name":"Virus diseases","url":"https://www.academia.edu/Documents/in/Virus_diseases?f_ri=24731","nofollow":true},{"id":2208075,"name":"Cysteine Proteinase Inhibitors","url":"https://www.academia.edu/Documents/in/Cysteine_Proteinase_Inhibitors?f_ri=24731","nofollow":true}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_13914805" data-work_id="13914805" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/13914805/Regulation_of_microRNA_1288_in_colorectal_cancer_Altered_expression_and_its_clinicopathological_significance">Regulation of microRNA‐1288 in colorectal cancer: Altered expression and its clinicopathological significance</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">We aim to examine the miR-1288 expression in cancer cell lines and a large cohort of patients with colorectal cancer. Two colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The miRNA... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_13914805" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">We aim to examine the miR-1288 expression in cancer cell lines and a large cohort of patients with colorectal cancer. Two colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The miRNA expressions of miR-1288 were tested on these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). An exogenous miR-1288 (mimic) was used to detect cell proliferation and cell cycle changes in SW480 using MTT calorimetric assay and flow cytometry, respectively. In addition, tissues from 122 patients with surgical resection of colorectum (82 adenocarcinomas, 20 adenomas, and 20 non-neoplastic tissues) were tested for miR-1288 expression by qRT-PCR. The colon cancer cell lines showed reduced expression of miR-1288 compared to normal colonic epithelial cell line. Over expression of miR-1288 in SW480 cell line showed increased cell proliferation and increased G2-M phase cells. In tissues, reduced miR-1288 expression was noted in majority of colorectal adenocarcinoma compared to colorectal adenoma and non-neoplastic tissues. Reduced or absent expression of miR-1288 was noted in 76% (n ¼ 62/82) of the cancers. The expression levels of miR-1288 were higher in distal colorectal adenocarcinomas (P ¼ 0.013) and in cancers of lower T staging (P ¼ 0.033). To conclude, alternation of miR-1288 expression is important in the progression of colorectal cancer. The differential regulation of miR-1288 was found to be related to cancer location and pathological staging in colorectal cancers. ß</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/13914805" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="839daa38d1ffce920d838d442e2ee0b0" rel="nofollow" data-download="{"attachment_id":44809067,"asset_id":13914805,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/44809067/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="32982398" href="https://tehran.academia.edu/ASalajegheh">A. 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Salajegheh","profile_url":"https://tehran.academia.edu/ASalajegheh?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_13914805 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="13914805"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 13914805, container: ".js-paper-rank-work_13914805", }); });</script></li><li class="js-percentile-work_13914805 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 13914805; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_13914805"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_13914805 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="13914805"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 13914805; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=13914805]").text(description); $(".js-view-count-work_13914805").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_13914805").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="13914805"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">18</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="3701" rel="nofollow" href="https://www.academia.edu/Documents/in/RNA">RNA</a>, <script data-card-contents-for-ri="3701" type="text/json">{"id":3701,"name":"RNA","url":"https://www.academia.edu/Documents/in/RNA?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="5490" rel="nofollow" href="https://www.academia.edu/Documents/in/MicroRNA">MicroRNA</a>, <script data-card-contents-for-ri="5490" type="text/json">{"id":5490,"name":"MicroRNA","url":"https://www.academia.edu/Documents/in/MicroRNA?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="6599" rel="nofollow" href="https://www.academia.edu/Documents/in/Flow_Cytometry">Flow Cytometry</a>, <script data-card-contents-for-ri="6599" type="text/json">{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="9113" rel="nofollow" href="https://www.academia.edu/Documents/in/Cell_Cycle">Cell Cycle</a><script data-card-contents-for-ri="9113" type="text/json">{"id":9113,"name":"Cell Cycle","url":"https://www.academia.edu/Documents/in/Cell_Cycle?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=13914805]'), work: {"id":13914805,"title":"Regulation of microRNA‐1288 in colorectal cancer: Altered expression and its clinicopathological significance","created_at":"2015-07-11T06:39:01.403-07:00","url":"https://www.academia.edu/13914805/Regulation_of_microRNA_1288_in_colorectal_cancer_Altered_expression_and_its_clinicopathological_significance?f_ri=24731","dom_id":"work_13914805","summary":"We aim to examine the miR-1288 expression in cancer cell lines and a large cohort of patients with colorectal cancer. Two colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The miRNA expressions of miR-1288 were tested on these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). An exogenous miR-1288 (mimic) was used to detect cell proliferation and cell cycle changes in SW480 using MTT calorimetric assay and flow cytometry, respectively. In addition, tissues from 122 patients with surgical resection of colorectum (82 adenocarcinomas, 20 adenomas, and 20 non-neoplastic tissues) were tested for miR-1288 expression by qRT-PCR. The colon cancer cell lines showed reduced expression of miR-1288 compared to normal colonic epithelial cell line. Over expression of miR-1288 in SW480 cell line showed increased cell proliferation and increased G2-M phase cells. In tissues, reduced miR-1288 expression was noted in majority of colorectal adenocarcinoma compared to colorectal adenoma and non-neoplastic tissues. Reduced or absent expression of miR-1288 was noted in 76% (n ¼ 62/82) of the cancers. The expression levels of miR-1288 were higher in distal colorectal adenocarcinomas (P ¼ 0.013) and in cancers of lower T staging (P ¼ 0.033). To conclude, alternation of miR-1288 expression is important in the progression of colorectal cancer. The differential regulation of miR-1288 was found to be related to cancer location and pathological staging in colorectal cancers. ß","downloadable_attachments":[{"id":44809067,"asset_id":13914805,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":32982398,"first_name":"A.","last_name":"Salajegheh","domain_name":"tehran","page_name":"ASalajegheh","display_name":"A. Salajegheh","profile_url":"https://tehran.academia.edu/ASalajegheh?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":3701,"name":"RNA","url":"https://www.academia.edu/Documents/in/RNA?f_ri=24731","nofollow":true},{"id":5490,"name":"MicroRNA","url":"https://www.academia.edu/Documents/in/MicroRNA?f_ri=24731","nofollow":true},{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry?f_ri=24731","nofollow":true},{"id":9113,"name":"Cell Cycle","url":"https://www.academia.edu/Documents/in/Cell_Cycle?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731"},{"id":37834,"name":"Western blotting","url":"https://www.academia.edu/Documents/in/Western_blotting?f_ri=24731"},{"id":137516,"name":"Follow-up studies","url":"https://www.academia.edu/Documents/in/Follow-up_studies?f_ri=24731"},{"id":289271,"name":"Aged","url":"https://www.academia.edu/Documents/in/Aged?f_ri=24731"},{"id":290569,"name":"Cultured meat","url":"https://www.academia.edu/Documents/in/Cultured_meat?f_ri=24731"},{"id":295854,"name":"microRNAs","url":"https://www.academia.edu/Documents/in/microRNAs?f_ri=24731"},{"id":424295,"name":"Survival Rate","url":"https://www.academia.edu/Documents/in/Survival_Rate?f_ri=24731"},{"id":489727,"name":"Prognosis","url":"https://www.academia.edu/Documents/in/Prognosis?f_ri=24731"},{"id":536979,"name":"MOLECULAR CARCİNOGENESİS","url":"https://www.academia.edu/Documents/in/MOLECULAR_CARC%C4%B0NOGENES%C4%B0S?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"},{"id":963748,"name":"Adenoma","url":"https://www.academia.edu/Documents/in/Adenoma?f_ri=24731"},{"id":1745478,"name":"Adenocarcinoma","url":"https://www.academia.edu/Documents/in/Adenocarcinoma?f_ri=24731"},{"id":1763968,"name":"Gene Expression Regulation","url":"https://www.academia.edu/Documents/in/Gene_Expression_Regulation?f_ri=24731"},{"id":2440562,"name":"Colorectal Neoplasms","url":"https://www.academia.edu/Documents/in/Colorectal_Neoplasms?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_14060243" data-work_id="14060243" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/14060243/Multicolored_redox_active_upconverter_cerium_oxide_nanoparticle_for_bio_imaging_and_therapeutics">Multicolored redox active upconverter cerium oxide nanoparticle for bio-imaging and therapeutics</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Cytocompatible, co-doped cerium oxide nanoparticles exhibited strong upconversion properties that were found to kill lung cancer cells by inducing apoptosis thereby demonstrating the potential to be used as clinical contrast agents for... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_14060243" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Cytocompatible, co-doped cerium oxide nanoparticles exhibited strong upconversion properties that were found to kill lung cancer cells by inducing apoptosis thereby demonstrating the potential to be used as clinical contrast agents for imaging and as therapeutic agents for treatment of cancer.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/14060243" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="4f7a8f862f002ba164e7ad51ed2cd009" rel="nofollow" data-download="{"attachment_id":44647996,"asset_id":14060243,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/44647996/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="33078335" href="https://independent.academia.edu/sureshbabu199">suresh babu</a><script data-card-contents-for-user="33078335" type="text/json">{"id":33078335,"first_name":"suresh","last_name":"babu","domain_name":"independent","page_name":"sureshbabu199","display_name":"suresh babu","profile_url":"https://independent.academia.edu/sureshbabu199?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_14060243 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="14060243"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 14060243, container: ".js-paper-rank-work_14060243", }); });</script></li><li class="js-percentile-work_14060243 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 14060243; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_14060243"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_14060243 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="14060243"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 14060243; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=14060243]").text(description); $(".js-view-count-work_14060243").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_14060243").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="14060243"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">12</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="13621" rel="nofollow" href="https://www.academia.edu/Documents/in/Nanoparticles">Nanoparticles</a>, <script data-card-contents-for-ri="13621" type="text/json">{"id":13621,"name":"Nanoparticles","url":"https://www.academia.edu/Documents/in/Nanoparticles?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="14054" rel="nofollow" href="https://www.academia.edu/Documents/in/Chemical">Chemical</a>, <script data-card-contents-for-ri="14054" type="text/json">{"id":14054,"name":"Chemical","url":"https://www.academia.edu/Documents/in/Chemical?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="71510" rel="nofollow" href="https://www.academia.edu/Documents/in/Endothelial_Cells">Endothelial Cells</a><script data-card-contents-for-ri="71510" type="text/json">{"id":71510,"name":"Endothelial Cells","url":"https://www.academia.edu/Documents/in/Endothelial_Cells?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=14060243]'), work: {"id":14060243,"title":"Multicolored redox active upconverter cerium oxide nanoparticle for bio-imaging and therapeutics","created_at":"2015-07-14T22:09:36.891-07:00","url":"https://www.academia.edu/14060243/Multicolored_redox_active_upconverter_cerium_oxide_nanoparticle_for_bio_imaging_and_therapeutics?f_ri=24731","dom_id":"work_14060243","summary":"Cytocompatible, co-doped cerium oxide nanoparticles exhibited strong upconversion properties that were found to kill lung cancer cells by inducing apoptosis thereby demonstrating the potential to be used as clinical contrast agents for imaging and as therapeutic agents for treatment of cancer.","downloadable_attachments":[{"id":44647996,"asset_id":14060243,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":33078335,"first_name":"suresh","last_name":"babu","domain_name":"independent","page_name":"sureshbabu199","display_name":"suresh babu","profile_url":"https://independent.academia.edu/sureshbabu199?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":13621,"name":"Nanoparticles","url":"https://www.academia.edu/Documents/in/Nanoparticles?f_ri=24731","nofollow":true},{"id":14054,"name":"Chemical","url":"https://www.academia.edu/Documents/in/Chemical?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":71510,"name":"Endothelial Cells","url":"https://www.academia.edu/Documents/in/Endothelial_Cells?f_ri=24731","nofollow":true},{"id":260118,"name":"CHEMICAL SCIENCES","url":"https://www.academia.edu/Documents/in/CHEMICAL_SCIENCES?f_ri=24731"},{"id":386276,"name":"Cerium","url":"https://www.academia.edu/Documents/in/Cerium?f_ri=24731"},{"id":390245,"name":"Particle Size","url":"https://www.academia.edu/Documents/in/Particle_Size?f_ri=24731"},{"id":440924,"name":"Surface Properties","url":"https://www.academia.edu/Documents/in/Surface_Properties?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival?f_ri=24731"},{"id":1212103,"name":"Antineoplastic Agents","url":"https://www.academia.edu/Documents/in/Antineoplastic_Agents?f_ri=24731"},{"id":1256747,"name":"Oxidation-Reduction","url":"https://www.academia.edu/Documents/in/Oxidation-Reduction?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_14112511" data-work_id="14112511" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/14112511/Receptor_tyrosine_kinases_exert_dominant_control_over_PI3K_signaling_in_human_KRAS_mutant_colorectal_cancers">Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Therapies inhibiting receptor tyrosine kinases (RTKs) are effective against some human cancers when they lead to simultaneous downregulation of PI3K/AKT and MEK/ERK signaling. However, mutant KRAS has the capacity to directly activate ERK... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_14112511" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Therapies inhibiting receptor tyrosine kinases (RTKs) are effective against some human cancers when they lead to simultaneous downregulation of PI3K/AKT and MEK/ERK signaling. However, mutant KRAS has the capacity to directly activate ERK and PI3K signaling, and this is thought to underlie the resistance of KRAS mutant cancers to RTK inhibitors. Here, we have elucidated the molecular regulation of both the PI3K/AKT and MEK/ERK signaling pathways in KRAS mutant colorectal cancer cells and identified combination therapies that lead to robust cancer cell apoptosis. KRAS knockdown using shRNA suppressed ERK signaling in all of the human KRAS mutant colorectal cancer cell lines examined. However, no decrease, and actually a modest increase, in AKT phosphorylation was often seen. By performing PI3K immunoprecipitations, we determined that RTKs, often IGF-IR, regulated PI3K signaling in the KRAS mutant cell lines. This conclusion was also supported by the observation that specific RTK inhibition led to marked suppression of PI3K signaling and biochemical assessment of patient specimens. Interestingly, combination of RTK and MEK inhibitors led to concomitant inhibition of PI3K and MEK signaling, marked growth suppression, and robust apoptosis of human KRAS mutant colorectal cancer cell lines in vitro and upon xenografting in mice. These findings provide a framework for utilizing RTK inhibitors in the treatment of KRAS mutant colorectal cancers.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/14112511" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="8b52446993060e9e023b526480e4f856" rel="nofollow" data-download="{"attachment_id":44592390,"asset_id":14112511,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/44592390/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="33114777" href="https://independent.academia.edu/EugeneLifshits">Eugene Lifshits</a><script data-card-contents-for-user="33114777" type="text/json">{"id":33114777,"first_name":"Eugene","last_name":"Lifshits","domain_name":"independent","page_name":"EugeneLifshits","display_name":"Eugene Lifshits","profile_url":"https://independent.academia.edu/EugeneLifshits?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_14112511 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="14112511"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 14112511, container: ".js-paper-rank-work_14112511", }); });</script></li><li class="js-percentile-work_14112511 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 14112511; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_14112511"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_14112511 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="14112511"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 14112511; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=14112511]").text(description); $(".js-view-count-work_14112511").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_14112511").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="14112511"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">8</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="38831" rel="nofollow" href="https://www.academia.edu/Documents/in/Signal_Transduction">Signal Transduction</a>, <script data-card-contents-for-ri="38831" type="text/json">{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="74780" rel="nofollow" href="https://www.academia.edu/Documents/in/Mutation">Mutation</a>, <script data-card-contents-for-ri="74780" type="text/json">{"id":74780,"name":"Mutation","url":"https://www.academia.edu/Documents/in/Mutation?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="84760" rel="nofollow" href="https://www.academia.edu/Documents/in/Mice">Mice</a><script data-card-contents-for-ri="84760" type="text/json">{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=14112511]'), work: {"id":14112511,"title":"Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers","created_at":"2015-07-16T06:54:13.549-07:00","url":"https://www.academia.edu/14112511/Receptor_tyrosine_kinases_exert_dominant_control_over_PI3K_signaling_in_human_KRAS_mutant_colorectal_cancers?f_ri=24731","dom_id":"work_14112511","summary":"Therapies inhibiting receptor tyrosine kinases (RTKs) are effective against some human cancers when they lead to simultaneous downregulation of PI3K/AKT and MEK/ERK signaling. However, mutant KRAS has the capacity to directly activate ERK and PI3K signaling, and this is thought to underlie the resistance of KRAS mutant cancers to RTK inhibitors. Here, we have elucidated the molecular regulation of both the PI3K/AKT and MEK/ERK signaling pathways in KRAS mutant colorectal cancer cells and identified combination therapies that lead to robust cancer cell apoptosis. KRAS knockdown using shRNA suppressed ERK signaling in all of the human KRAS mutant colorectal cancer cell lines examined. However, no decrease, and actually a modest increase, in AKT phosphorylation was often seen. By performing PI3K immunoprecipitations, we determined that RTKs, often IGF-IR, regulated PI3K signaling in the KRAS mutant cell lines. This conclusion was also supported by the observation that specific RTK inhibition led to marked suppression of PI3K signaling and biochemical assessment of patient specimens. Interestingly, combination of RTK and MEK inhibitors led to concomitant inhibition of PI3K and MEK signaling, marked growth suppression, and robust apoptosis of human KRAS mutant colorectal cancer cell lines in vitro and upon xenografting in mice. These findings provide a framework for utilizing RTK inhibitors in the treatment of KRAS mutant colorectal cancers.","downloadable_attachments":[{"id":44592390,"asset_id":14112511,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":33114777,"first_name":"Eugene","last_name":"Lifshits","domain_name":"independent","page_name":"EugeneLifshits","display_name":"Eugene Lifshits","profile_url":"https://independent.academia.edu/EugeneLifshits?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true},{"id":74780,"name":"Mutation","url":"https://www.academia.edu/Documents/in/Mutation?f_ri=24731","nofollow":true},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731","nofollow":true},{"id":809882,"name":"Base Sequence","url":"https://www.academia.edu/Documents/in/Base_Sequence?f_ri=24731"},{"id":1144154,"name":"Clinical Investigation","url":"https://www.academia.edu/Documents/in/Clinical_Investigation?f_ri=24731"},{"id":1343089,"name":"Protein Kinase Inhibitors","url":"https://www.academia.edu/Documents/in/Protein_Kinase_Inhibitors?f_ri=24731"},{"id":2440562,"name":"Colorectal Neoplasms","url":"https://www.academia.edu/Documents/in/Colorectal_Neoplasms?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_22651569" data-work_id="22651569" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/22651569/Effects_of_Glucose_Insulin_and_Supernatant_from_Pancreatic_%CE%B2_cells_on_Brain_Pancreas_Relative_Protein_in_Rat_Hippocampus">Effects of Glucose, Insulin, and Supernatant from Pancreatic β-cells on Brain–Pancreas Relative Protein in Rat Hippocampus</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Brain-pancreas relative protein (BPRP) is a novel protein that mainly expresses in brain and pancreas. In our previous study, we found that various stressors significantly decreased the expression of BPRP in pancreas in vivo, accompanied... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_22651569" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Brain-pancreas relative protein (BPRP) is a novel protein that mainly expresses in brain and pancreas. In our previous study, we found that various stressors significantly decreased the expression of BPRP in pancreas in vivo, accompanied by changes in insulin and glucose levels, and that expression of BPRP in pancreas also decreased significantly in diabetic rats induced by Streptozocin (STZ). All these findings suggest that BPRP may be a glucose or insulinsensitive protein. However, how the changes in insulin or glucose levels influence the expression of BPRP in hippocampus requires further study. Here, we investigated the effects of insulin or glucose on the expression of BPRP in primary cultured hippocampal neurons. We supplied hippocampal neurons with glucose, insulin, or supernatant from pancreatic b-cells, which secrete insulin into the supernatant. Our data showed that insulin had beneficial effect on the viability while no significant effect on the expression of BPRP in hippocampal neurons. On the contrary, 40 mM glucose or free glucose culture significantly decreased the expression of BPRP, while had no significant effect on the viability and apoptosis of hippocampal neurons. Further study showed that levels of insulin in the supernatant collected from pancreatic b-cells medium changed over days, and that supernatant increased the viability of hippocampal neurons, while it had no obvious effect on the expression of BPRP in hippocampal neurons. These results suggest that BPRP may be a glucose-sensitive protein.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/22651569" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="ee45fbe10c9ffa5103ccb999b0c2e740" rel="nofollow" data-download="{"attachment_id":43242820,"asset_id":22651569,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/43242820/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="32828281" href="https://rug.academia.edu/GertTerHorst">Gert J ter Horst</a><script data-card-contents-for-user="32828281" type="text/json">{"id":32828281,"first_name":"Gert","last_name":"ter Horst","domain_name":"rug","page_name":"GertTerHorst","display_name":"Gert J ter Horst","profile_url":"https://rug.academia.edu/GertTerHorst?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_22651569 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="22651569"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 22651569, container: ".js-paper-rank-work_22651569", }); 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$(".js-view-count[data-work-id=22651569]").text(description); $(".js-view-count-work_22651569").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_22651569").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="22651569"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">15</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="6599" rel="nofollow" href="https://www.academia.edu/Documents/in/Flow_Cytometry">Flow Cytometry</a>, <script data-card-contents-for-ri="6599" type="text/json">{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="18533" rel="nofollow" href="https://www.academia.edu/Documents/in/Confocal_Microscopy">Confocal Microscopy</a>, <script data-card-contents-for-ri="18533" type="text/json">{"id":18533,"name":"Confocal Microscopy","url":"https://www.academia.edu/Documents/in/Confocal_Microscopy?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="47884" rel="nofollow" href="https://www.academia.edu/Documents/in/Biological_Sciences">Biological Sciences</a><script data-card-contents-for-ri="47884" type="text/json">{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=22651569]'), work: {"id":22651569,"title":"Effects of Glucose, Insulin, and Supernatant from Pancreatic β-cells on Brain–Pancreas Relative Protein in Rat Hippocampus","created_at":"2016-03-01T07:21:09.215-08:00","url":"https://www.academia.edu/22651569/Effects_of_Glucose_Insulin_and_Supernatant_from_Pancreatic_%CE%B2_cells_on_Brain_Pancreas_Relative_Protein_in_Rat_Hippocampus?f_ri=24731","dom_id":"work_22651569","summary":"Brain-pancreas relative protein (BPRP) is a novel protein that mainly expresses in brain and pancreas. In our previous study, we found that various stressors significantly decreased the expression of BPRP in pancreas in vivo, accompanied by changes in insulin and glucose levels, and that expression of BPRP in pancreas also decreased significantly in diabetic rats induced by Streptozocin (STZ). All these findings suggest that BPRP may be a glucose or insulinsensitive protein. However, how the changes in insulin or glucose levels influence the expression of BPRP in hippocampus requires further study. Here, we investigated the effects of insulin or glucose on the expression of BPRP in primary cultured hippocampal neurons. We supplied hippocampal neurons with glucose, insulin, or supernatant from pancreatic b-cells, which secrete insulin into the supernatant. Our data showed that insulin had beneficial effect on the viability while no significant effect on the expression of BPRP in hippocampal neurons. On the contrary, 40 mM glucose or free glucose culture significantly decreased the expression of BPRP, while had no significant effect on the viability and apoptosis of hippocampal neurons. Further study showed that levels of insulin in the supernatant collected from pancreatic b-cells medium changed over days, and that supernatant increased the viability of hippocampal neurons, while it had no obvious effect on the expression of BPRP in hippocampal neurons. These results suggest that BPRP may be a glucose-sensitive protein.","downloadable_attachments":[{"id":43242820,"asset_id":22651569,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":32828281,"first_name":"Gert","last_name":"ter Horst","domain_name":"rug","page_name":"GertTerHorst","display_name":"Gert J ter Horst","profile_url":"https://rug.academia.edu/GertTerHorst?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry?f_ri=24731","nofollow":true},{"id":18533,"name":"Confocal Microscopy","url":"https://www.academia.edu/Documents/in/Confocal_Microscopy?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences?f_ri=24731","nofollow":true},{"id":57556,"name":"Hippocampus","url":"https://www.academia.edu/Documents/in/Hippocampus?f_ri=24731"},{"id":71289,"name":"Glucose","url":"https://www.academia.edu/Documents/in/Glucose?f_ri=24731"},{"id":71400,"name":"Insulin","url":"https://www.academia.edu/Documents/in/Insulin?f_ri=24731"},{"id":193974,"name":"Neurons","url":"https://www.academia.edu/Documents/in/Neurons?f_ri=24731"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats?f_ri=24731"},{"id":453923,"name":"Oral Hypoglycemic Agents","url":"https://www.academia.edu/Documents/in/Oral_Hypoglycemic_Agents?f_ri=24731"},{"id":782254,"name":"Primary Culture","url":"https://www.academia.edu/Documents/in/Primary_Culture?f_ri=24731"},{"id":806503,"name":"Thiazoles","url":"https://www.academia.edu/Documents/in/Thiazoles?f_ri=24731"},{"id":1031967,"name":"Diabetic Rat","url":"https://www.academia.edu/Documents/in/Diabetic_Rat?f_ri=24731"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival?f_ri=24731"},{"id":1991090,"name":"Neurochemical","url":"https://www.academia.edu/Documents/in/Neurochemical?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_20122565" data-work_id="20122565" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/20122565/Levosimendan_Protection_against_Kidney_Ischemia_Reperfusion_Injuries_in_Anesthetized_Pigs">Levosimendan Protection against Kidney Ischemia/Reperfusion Injuries in Anesthetized Pigs</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Ischemia/reperfusion (I/R) injury is an important cause of acute renal failure because of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine any possible protective effects of levosimendan in an... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_20122565" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Ischemia/reperfusion (I/R) injury is an important cause of acute renal failure because of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine any possible protective effects of levosimendan in an in vivo pig model of renal I/R injury. In 40 anesthetized pigs (eight groups of five pigs each), I/R was induced by clamping-reopening the left renal artery. During ischemia, in three groups of pigs, levosimendan and the multiorgan preservation solution Custodiol, alone or in combination with levosimendan, were infused in the renal artery. In two other groups of animals, levosimendan in combination with Custodiol was administered after the intrarenal nitric-oxide (NO) synthase blocker N -nitro-L-arginine methyl ester (L-NAME) or the mitochondrial ATP-sensitive K ϩ channel (K ATP channel) inhibitor 5-hydroxydecanoate (5-HD). In the other animals, saline, L-NAME, or 5-HD were administered alone. Throughout the experiments, urinary N-acetyl-␤-glucosaminidase (NAG) release was measured, and renal function was assessed. Moreover, renal biopsy samples were taken for the detection of apoptosis and tissue peroxidation. In pigs treated with levosimendan or the combination of levosimendan and Custodiol, NAG, peroxidation, and apoptotic markers were lower than in animals treated with Custodiol alone. In addition, renal function was better preserved, and cell survival and antioxidant systems were more activated. All beneficial effects were prevented by L-NAME and 5-HD. In conclusion, levosimendan alone or in combination with Custodiol exerted better protection against renal I/R injuries than Custodiol alone through antioxidant, antiapoptotic, and prosurvival actions depending on mitochondrial K ATP channels and NO-related mechanisms.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/20122565" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="fc9c4495b7efbc69dab4e2e3eb1c73d7" rel="nofollow" data-download="{"attachment_id":41189477,"asset_id":20122565,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/41189477/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="41183895" href="https://independent.academia.edu/EGrossini">E. Grossini</a><script data-card-contents-for-user="41183895" type="text/json">{"id":41183895,"first_name":"E.","last_name":"Grossini","domain_name":"independent","page_name":"EGrossini","display_name":"E. 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The aim of the present study was to examine any possible protective effects of levosimendan in an in vivo pig model of renal I/R injury. In 40 anesthetized pigs (eight groups of five pigs each), I/R was induced by clamping-reopening the left renal artery. During ischemia, in three groups of pigs, levosimendan and the multiorgan preservation solution Custodiol, alone or in combination with levosimendan, were infused in the renal artery. In two other groups of animals, levosimendan in combination with Custodiol was administered after the intrarenal nitric-oxide (NO) synthase blocker N -nitro-L-arginine methyl ester (L-NAME) or the mitochondrial ATP-sensitive K ϩ channel (K ATP channel) inhibitor 5-hydroxydecanoate (5-HD). In the other animals, saline, L-NAME, or 5-HD were administered alone. Throughout the experiments, urinary N-acetyl-␤-glucosaminidase (NAG) release was measured, and renal function was assessed. Moreover, renal biopsy samples were taken for the detection of apoptosis and tissue peroxidation. In pigs treated with levosimendan or the combination of levosimendan and Custodiol, NAG, peroxidation, and apoptotic markers were lower than in animals treated with Custodiol alone. In addition, renal function was better preserved, and cell survival and antioxidant systems were more activated. All beneficial effects were prevented by L-NAME and 5-HD. In conclusion, levosimendan alone or in combination with Custodiol exerted better protection against renal I/R injuries than Custodiol alone through antioxidant, antiapoptotic, and prosurvival actions depending on mitochondrial K ATP channels and NO-related mechanisms.","downloadable_attachments":[{"id":41189477,"asset_id":20122565,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":41183895,"first_name":"E.","last_name":"Grossini","domain_name":"independent","page_name":"EGrossini","display_name":"E. Grossini","profile_url":"https://independent.academia.edu/EGrossini?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":9000,"name":"Acute kidney injury","url":"https://www.academia.edu/Documents/in/Acute_kidney_injury?f_ri=24731","nofollow":true},{"id":15719,"name":"Mitochondria","url":"https://www.academia.edu/Documents/in/Mitochondria?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":51711,"name":"Antioxidants","url":"https://www.academia.edu/Documents/in/Antioxidants?f_ri=24731","nofollow":true},{"id":71289,"name":"Glucose","url":"https://www.academia.edu/Documents/in/Glucose?f_ri=24731"},{"id":71294,"name":"Kidney","url":"https://www.academia.edu/Documents/in/Kidney?f_ri=24731"},{"id":93922,"name":"Nitric oxide","url":"https://www.academia.edu/Documents/in/Nitric_oxide?f_ri=24731"},{"id":362533,"name":"Hydrazones","url":"https://www.academia.edu/Documents/in/Hydrazones?f_ri=24731"},{"id":382388,"name":"Nitric Oxide Synthase","url":"https://www.academia.edu/Documents/in/Nitric_Oxide_Synthase?f_ri=24731"},{"id":419370,"name":"Swine","url":"https://www.academia.edu/Documents/in/Swine?f_ri=24731"},{"id":794984,"name":"Reperfusion injury","url":"https://www.academia.edu/Documents/in/Reperfusion_injury?f_ri=24731"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival?f_ri=24731"},{"id":1295914,"name":"Potassium Chloride","url":"https://www.academia.edu/Documents/in/Potassium_Chloride?f_ri=24731"},{"id":1703031,"name":"Mannitol","url":"https://www.academia.edu/Documents/in/Mannitol?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_20085203 coauthored" data-work_id="20085203" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/20085203/ImmunoPET_imaging_of_phosphatidylserine_in_pro_apoptotic_therapy_treated_tumor_models">ImmunoPET imaging of phosphatidylserine in pro-apoptotic therapy treated tumor models</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">An immunoPET imaging probe for the detection of phosphatidylserine was developed and tested in animal models of human cancer treated with pro-apoptotic therapy. We hypothesized that the relatively long plasma half-life of a probe based on... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_20085203" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">An immunoPET imaging probe for the detection of phosphatidylserine was developed and tested in animal models of human cancer treated with pro-apoptotic therapy. We hypothesized that the relatively long plasma half-life of a probe based on a full-length antibody coupled with a residualizing radionuclide would be able to catch the wave of drug-induced apoptosis and lead to a specific accumulation in apoptotic tumor tissue.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/20085203" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="ca04bec991dc46ec708a5f1871547527" rel="nofollow" data-download="{"attachment_id":41231270,"asset_id":20085203,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/41231270/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="41094082" href="https://independent.academia.edu/AnnieOgasawara">Annie Ogasawara</a><script data-card-contents-for-user="41094082" type="text/json">{"id":41094082,"first_name":"Annie","last_name":"Ogasawara","domain_name":"independent","page_name":"AnnieOgasawara","display_name":"Annie Ogasawara","profile_url":"https://independent.academia.edu/AnnieOgasawara?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-20085203">+3</span><div class="hidden js-additional-users-20085203"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://independent.academia.edu/AshkenaziAvi">Avi Ashkenazi</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://independent.academia.edu/JudithFlores7">Judith Flores</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://independent.academia.edu/JeffTinianow">Jeff Tinianow</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-20085203'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-20085203').html(); 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container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_20085203 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="20085203"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 20085203; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=20085203]").text(description); $(".js-view-count-work_20085203").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_20085203").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="20085203"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">6</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="23518" rel="nofollow" href="https://www.academia.edu/Documents/in/Positron_Emission_Tomography">Positron Emission Tomography</a>, <script data-card-contents-for-ri="23518" type="text/json">{"id":23518,"name":"Positron Emission Tomography","url":"https://www.academia.edu/Documents/in/Positron_Emission_Tomography?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="147196" rel="nofollow" href="https://www.academia.edu/Documents/in/Monoclonal_Antibodies">Monoclonal Antibodies</a>, <script data-card-contents-for-ri="147196" type="text/json">{"id":147196,"name":"Monoclonal Antibodies","url":"https://www.academia.edu/Documents/in/Monoclonal_Antibodies?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="244814" rel="nofollow" href="https://www.academia.edu/Documents/in/Clinical_Sciences">Clinical Sciences</a><script data-card-contents-for-ri="244814" type="text/json">{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=20085203]'), work: {"id":20085203,"title":"ImmunoPET imaging of phosphatidylserine in pro-apoptotic therapy treated tumor models","created_at":"2016-01-07T10:59:14.877-08:00","url":"https://www.academia.edu/20085203/ImmunoPET_imaging_of_phosphatidylserine_in_pro_apoptotic_therapy_treated_tumor_models?f_ri=24731","dom_id":"work_20085203","summary":"An immunoPET imaging probe for the detection of phosphatidylserine was developed and tested in animal models of human cancer treated with pro-apoptotic therapy. 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Sox2 can act synergistically with Oct3/4 in vitro to activate Oct-Sox enhancers, which regulate the expression of pluripotent stem cellspecific genes, including Nanog, Oct3/4 and Sox2 itself. These findings... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_30680028" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Sox2 has yet to be determined. Sox2 can act synergistically with Oct3/4 in vitro to activate Oct-Sox enhancers, which regulate the expression of pluripotent stem cellspecific genes, including Nanog, Oct3/4 and Sox2 itself. These findings suggest that Sox2 is required by ES cells for its Oct-Sox enhancer activity. Using inducible Sox2-null mouse ES cells, we show that Sox2 is dispensable for the activation of these Oct-Sox enhancers. In contrast, we demonstrate that Sox2 is necessary for regulating multiple transcription factors that affect Oct3/4 expression and that the forced expression of Oct3/4 rescues the pluripotency of Sox2-null ES cells. These results indicate that the essential function of Sox2 is to stabilize ES cells in a pluripotent state by maintaining the requisite level of Oct3/4 expression.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/30680028" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="13e50be489ce54ab24a96b8cd2165b8f" rel="nofollow" data-download="{"attachment_id":51121395,"asset_id":30680028,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/51121395/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="178717" href="https://nih.academia.edu/AlexeiSharov">Alexei Sharov</a><script data-card-contents-for-user="178717" type="text/json">{"id":178717,"first_name":"Alexei","last_name":"Sharov","domain_name":"nih","page_name":"AlexeiSharov","display_name":"Alexei Sharov","profile_url":"https://nih.academia.edu/AlexeiSharov?f_ri=24731","photo":"https://0.academia-photos.com/178717/15356776/16001216/s65_alexei.sharov.jpg"}</script></span></span></li><li class="js-paper-rank-work_30680028 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="30680028"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 30680028, container: ".js-paper-rank-work_30680028", }); 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$(".js-view-count[data-work-id=30680028]").text(description); $(".js-view-count-work_30680028").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_30680028").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="30680028"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">34</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="145" rel="nofollow" href="https://www.academia.edu/Documents/in/Biochemistry">Biochemistry</a>, <script data-card-contents-for-ri="145" type="text/json">{"id":145,"name":"Biochemistry","url":"https://www.academia.edu/Documents/in/Biochemistry?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="156" rel="nofollow" href="https://www.academia.edu/Documents/in/Genetics">Genetics</a>, <script data-card-contents-for-ri="156" type="text/json">{"id":156,"name":"Genetics","url":"https://www.academia.edu/Documents/in/Genetics?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="502" rel="nofollow" href="https://www.academia.edu/Documents/in/Biophysics">Biophysics</a>, <script data-card-contents-for-ri="502" type="text/json">{"id":502,"name":"Biophysics","url":"https://www.academia.edu/Documents/in/Biophysics?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="2513" rel="nofollow" href="https://www.academia.edu/Documents/in/Molecular_Biology">Molecular Biology</a><script data-card-contents-for-ri="2513" type="text/json">{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=30680028]'), work: {"id":30680028,"title":"Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells","created_at":"2016-12-30T07:29:03.340-08:00","url":"https://www.academia.edu/30680028/Pluripotency_governed_by_Sox2_via_regulation_of_Oct3_4_expression_in_mouse_embryonic_stem_cells?f_ri=24731","dom_id":"work_30680028","summary":"Sox2 has yet to be determined. Sox2 can act synergistically with Oct3/4 in vitro to activate Oct-Sox enhancers, which regulate the expression of pluripotent stem cellspecific genes, including Nanog, Oct3/4 and Sox2 itself. These findings suggest that Sox2 is required by ES cells for its Oct-Sox enhancer activity. Using inducible Sox2-null mouse ES cells, we show that Sox2 is dispensable for the activation of these Oct-Sox enhancers. In contrast, we demonstrate that Sox2 is necessary for regulating multiple transcription factors that affect Oct3/4 expression and that the forced expression of Oct3/4 rescues the pluripotency of Sox2-null ES cells. These results indicate that the essential function of Sox2 is to stabilize ES cells in a pluripotent state by maintaining the requisite level of Oct3/4 expression.","downloadable_attachments":[{"id":51121395,"asset_id":30680028,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":178717,"first_name":"Alexei","last_name":"Sharov","domain_name":"nih","page_name":"AlexeiSharov","display_name":"Alexei Sharov","profile_url":"https://nih.academia.edu/AlexeiSharov?f_ri=24731","photo":"https://0.academia-photos.com/178717/15356776/16001216/s65_alexei.sharov.jpg"}],"research_interests":[{"id":145,"name":"Biochemistry","url":"https://www.academia.edu/Documents/in/Biochemistry?f_ri=24731","nofollow":true},{"id":156,"name":"Genetics","url":"https://www.academia.edu/Documents/in/Genetics?f_ri=24731","nofollow":true},{"id":502,"name":"Biophysics","url":"https://www.academia.edu/Documents/in/Biophysics?f_ri=24731","nofollow":true},{"id":2513,"name":"Molecular 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Although the familiarization and dependency of mobile phones is growing at an alarming pace, the biological effects due... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_76615751" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Wireless technologies are ubiquitous today and the mobile phones are one of the prodigious output of this technology. Although the familiarization and dependency of mobile phones is growing at an alarming pace, the biological effects due to the exposure of radiations have become a subject of intense debate. The present evidence on mobile phone radiation exposure is based on scientific research and public policy initiative to give an overview of what is known of biological effects that occur at radiofrequency (RF)/ electromagnetic fields (EMFs) exposure. The conflict in conclusions is mainly because of difficulty in controlling the affecting parameters. Biological effects are dependent not only on the distance and size of the object (with respect to the object) but also on the environmental parameters. Health endpoints reported to be associated with RF include childhood leukemia, brain tumors, genotoxic effects, neurological effects and neurodegenerative diseases, immune system dereg...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/76615751" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="fada471593df862ca48f8eab0d20081c" rel="nofollow" data-download="{"attachment_id":84266301,"asset_id":76615751,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/84266301/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="1192228" href="https://jnu.academia.edu/ramovatarmeena">ramovatar meena</a><script data-card-contents-for-user="1192228" type="text/json">{"id":1192228,"first_name":"ramovatar","last_name":"meena","domain_name":"jnu","page_name":"ramovatarmeena","display_name":"ramovatar meena","profile_url":"https://jnu.academia.edu/ramovatarmeena?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_76615751 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="76615751"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 76615751, container: ".js-paper-rank-work_76615751", }); 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js-work-card work_76265930" data-work_id="76265930" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/76265930/Increased_expression_of_stem_cell_markers_in_malignant_melanoma">Increased expression of stem cell markers in malignant melanoma</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">The potential role of stem cells in neoplasia is a subject of recent interest. Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_76265930" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">The potential role of stem cells in neoplasia is a subject of recent interest. Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. CD133 is expressed on the surface of dermal-derived stem cells that are capable of differentiating into neural cells. Nestin is an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells. In this study, we evaluate the expression of these markers and possible differences among banal nevi, primary melanoma, and metastastic melanoma. Tissue microarrays containing normal tissue and 226 melanocytic lesions (71 banal nevi, 71 in situ and invasive melanomas, and 84 metastatic melanomas) were studied by immunohistochemistry using monoclonal antibodies CD166, CD133, and nestin. A significantly greater percentage of melanomas (combined primary and metastatic) contained cells that expressed CD166 (P ¼ 0.005), CD133 (P ¼ 0.003), and nestin (P ¼ 0.03) than banal nevi. Only nestin showed a statistical difference when comparing primary and metastatic melanoma (P ¼ 0.05). A stepwise increase in the proportion of lesions expressing all three markers was observed from banal nevi (2/19) to primary melanomas (8/17) to metastatic melanoma (19/28), P ¼ 0.0005. All cases of metastatic melanoma expressed at least one stem cell marker. The increased expression of CD166, CD133, and nestin in melanoma suggests that progression to malignant melanoma likely involves genetic pathways instrumental to stem cell biology and normal tissue development. Further studies and characterization of these pathways may also reveal new prognostic markers for a disease whose prognosis in advanced stages is dismal.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/76265930" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="fd537061a2b8541ce43f189c45553996" rel="nofollow" data-download="{"attachment_id":84025846,"asset_id":76265930,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/84025846/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="33313647" href="https://independent.academia.edu/HongWu6">Hong Wu</a><script data-card-contents-for-user="33313647" type="text/json">{"id":33313647,"first_name":"Hong","last_name":"Wu","domain_name":"independent","page_name":"HongWu6","display_name":"Hong Wu","profile_url":"https://independent.academia.edu/HongWu6?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_76265930 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="76265930"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 76265930, container: ".js-paper-rank-work_76265930", }); 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Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. CD133 is expressed on the surface of dermal-derived stem cells that are capable of differentiating into neural cells. Nestin is an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells. In this study, we evaluate the expression of these markers and possible differences among banal nevi, primary melanoma, and metastastic melanoma. Tissue microarrays containing normal tissue and 226 melanocytic lesions (71 banal nevi, 71 in situ and invasive melanomas, and 84 metastatic melanomas) were studied by immunohistochemistry using monoclonal antibodies CD166, CD133, and nestin. A significantly greater percentage of melanomas (combined primary and metastatic) contained cells that expressed CD166 (P ¼ 0.005), CD133 (P ¼ 0.003), and nestin (P ¼ 0.03) than banal nevi. Only nestin showed a statistical difference when comparing primary and metastatic melanoma (P ¼ 0.05). A stepwise increase in the proportion of lesions expressing all three markers was observed from banal nevi (2/19) to primary melanomas (8/17) to metastatic melanoma (19/28), P ¼ 0.0005. All cases of metastatic melanoma expressed at least one stem cell marker. The increased expression of CD166, CD133, and nestin in melanoma suggests that progression to malignant melanoma likely involves genetic pathways instrumental to stem cell biology and normal tissue development. Further studies and characterization of these pathways may also reveal new prognostic markers for a disease whose prognosis in advanced stages is dismal.","downloadable_attachments":[{"id":84025846,"asset_id":76265930,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":33313647,"first_name":"Hong","last_name":"Wu","domain_name":"independent","page_name":"HongWu6","display_name":"Hong 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u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Historical perspective Asthma is a disease whose ability to cause episodic symptomatology has been appreciated since antiquity. Although the fine points of the definition can be debated, it is reasonable to think of asthma as a pulmonary... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_65680240" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Historical perspective Asthma is a disease whose ability to cause episodic symptomatology has been appreciated since antiquity. Although the fine points of the definition can be debated, it is reasonable to think of asthma as a pulmonary disorder characterized by the generalized reversible obstruction of airflow and to define reversibility as a greater than 12% increase in the patient's forced expiratory volume in 1 second (FEV 1) that occurs either spontaneously or with therapy. Airway hyperresponsiveness, an exaggerated bronchospastic response to nonspecific agents such as methacholine and histamine or specific antigens, is the physiologic cornerstone of this disorder. A diagnosis of asthma is established based on a history of recurrent wheeze, cough, or shortness of breath, reversible airway obstruction demonstrated by pulmonary-function testing, and, in cases where questions exist, a methacholine challenge demonstrating airway hyperresponsiveness. It has long been assumed that patients with asthma experience intermittent attacks and have relatively normal lung function during intervening periods. More recent studies have demonstrated that asthma can cause progressive lung impairment and, in some patients, eventuate in partially reversible or irreversible airway obstruction. Any discussion of asthma must take into account the recent increase in its prevalence. Since approximately 1980, the frequency of this disorder has almost doubled. As a result of this "epidemic," asthma now affects approximately 8-10% of the population in the US, is the leading cause of hospitalization among children less than 15 years of age, and costs society billions of dollars annually. This increase in prevalence is not simply due to diagnostic transference or increased diagnostic awareness, since asthma mortality rates have also increased during this interval.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/65680240" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="27788bff7e9c940ec153ffb901a4acb2" rel="nofollow" data-download="{"attachment_id":77172247,"asset_id":65680240,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/77172247/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="33159209" href="https://independent.academia.edu/JackaElias">Jack a. Elias</a><script data-card-contents-for-user="33159209" type="text/json">{"id":33159209,"first_name":"Jack a.","last_name":"Elias","domain_name":"independent","page_name":"JackaElias","display_name":"Jack a. Elias","profile_url":"https://independent.academia.edu/JackaElias?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_65680240 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="65680240"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 65680240, container: ".js-paper-rank-work_65680240", }); });</script></li><li class="js-percentile-work_65680240 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 65680240; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_65680240"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_65680240 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="65680240"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 65680240; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=65680240]").text(description); $(".js-view-count-work_65680240").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_65680240").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="65680240"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">14</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="9968" rel="nofollow" href="https://www.academia.edu/Documents/in/Asthma">Asthma</a>, <script data-card-contents-for-ri="9968" type="text/json">{"id":9968,"name":"Asthma","url":"https://www.academia.edu/Documents/in/Asthma?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="26327" rel="nofollow" href="https://www.academia.edu/Documents/in/Medicine">Medicine</a>, <script data-card-contents-for-ri="26327" type="text/json">{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="38831" rel="nofollow" href="https://www.academia.edu/Documents/in/Signal_Transduction">Signal Transduction</a><script data-card-contents-for-ri="38831" type="text/json">{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=65680240]'), work: {"id":65680240,"title":"New insights into the pathogenesis of asthma","created_at":"2021-12-23T05:21:35.174-08:00","url":"https://www.academia.edu/65680240/New_insights_into_the_pathogenesis_of_asthma?f_ri=24731","dom_id":"work_65680240","summary":"Historical perspective Asthma is a disease whose ability to cause episodic symptomatology has been appreciated since antiquity. Although the fine points of the definition can be debated, it is reasonable to think of asthma as a pulmonary disorder characterized by the generalized reversible obstruction of airflow and to define reversibility as a greater than 12% increase in the patient's forced expiratory volume in 1 second (FEV 1) that occurs either spontaneously or with therapy. Airway hyperresponsiveness, an exaggerated bronchospastic response to nonspecific agents such as methacholine and histamine or specific antigens, is the physiologic cornerstone of this disorder. A diagnosis of asthma is established based on a history of recurrent wheeze, cough, or shortness of breath, reversible airway obstruction demonstrated by pulmonary-function testing, and, in cases where questions exist, a methacholine challenge demonstrating airway hyperresponsiveness. It has long been assumed that patients with asthma experience intermittent attacks and have relatively normal lung function during intervening periods. More recent studies have demonstrated that asthma can cause progressive lung impairment and, in some patients, eventuate in partially reversible or irreversible airway obstruction. Any discussion of asthma must take into account the recent increase in its prevalence. Since approximately 1980, the frequency of this disorder has almost doubled. As a result of this \"epidemic,\" asthma now affects approximately 8-10% of the population in the US, is the leading cause of hospitalization among children less than 15 years of age, and costs society billions of dollars annually. This increase in prevalence is not simply due to diagnostic transference or increased diagnostic awareness, since asthma mortality rates have also increased during this interval.","downloadable_attachments":[{"id":77172247,"asset_id":65680240,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":33159209,"first_name":"Jack a.","last_name":"Elias","domain_name":"independent","page_name":"JackaElias","display_name":"Jack a. Elias","profile_url":"https://independent.academia.edu/JackaElias?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":9968,"name":"Asthma","url":"https://www.academia.edu/Documents/in/Asthma?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine?f_ri=24731","nofollow":true},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction?f_ri=24731","nofollow":true},{"id":50841,"name":"Caspases","url":"https://www.academia.edu/Documents/in/Caspases?f_ri=24731"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":93922,"name":"Nitric oxide","url":"https://www.academia.edu/Documents/in/Nitric_oxide?f_ri=24731"},{"id":99708,"name":"Clinical","url":"https://www.academia.edu/Documents/in/Clinical?f_ri=24731"},{"id":371516,"name":"Eosinophils","url":"https://www.academia.edu/Documents/in/Eosinophils?f_ri=24731"},{"id":1144154,"name":"Clinical Investigation","url":"https://www.academia.edu/Documents/in/Clinical_Investigation?f_ri=24731"},{"id":1180711,"name":"Eosinophilia","url":"https://www.academia.edu/Documents/in/Eosinophilia?f_ri=24731"},{"id":1763968,"name":"Gene Expression Regulation","url":"https://www.academia.edu/Documents/in/Gene_Expression_Regulation?f_ri=24731"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin?f_ri=24731"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_65035698" data-work_id="65035698" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/65035698/Regular_and_moderate_exercise_before_experimental_sepsis_reduces_the_risk_of_lung_and_distal_organ_injury">Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Physical activity modulates inflammation and immune response in both normal and pathologic conditions. We investigated whether regular and moderate exercise before the induction of experimental sepsis reduces the risk of lung and distal... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_65035698" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Physical activity modulates inflammation and immune response in both normal and pathologic conditions. We investigated whether regular and moderate exercise before the induction of experimental sepsis reduces the risk of lung and distal organ injury and survival. One hundred twenty-four BALB/c mice were randomly assigned to two groups: sedentary (S) and trained (T). Animals in T group ran on a motorized treadmill, at moderate intensity, 5% grade, 30 min/day, 3 times a week for 8 wk. Cardiac adaptation to exercise was evaluated using echocardiography. Systolic volume and left ventricular mass were increased in T compared with S group. Both T and S groups were further randomized either to sepsis induced by cecal ligation and puncture surgery (CLP) or sham operation (control). After 24 h, lung mechanics and histology, the degree of cell apoptosis in lung, heart, kidney, liver, and small intestine villi, and interleukin (IL)-6, KC (IL-8 murine functional homolog), IL-1β, IL-10, and numb...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/65035698" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="254db17a2a79233505d4ad4f52dfacdd" rel="nofollow" data-download="{"attachment_id":76796253,"asset_id":65035698,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/76796253/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="40789040" href="https://independent.academia.edu/NazarethRocha">Nazareth Rocha</a><script data-card-contents-for-user="40789040" type="text/json">{"id":40789040,"first_name":"Nazareth","last_name":"Rocha","domain_name":"independent","page_name":"NazarethRocha","display_name":"Nazareth Rocha","profile_url":"https://independent.academia.edu/NazarethRocha?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_65035698 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="65035698"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 65035698, container: ".js-paper-rank-work_65035698", }); });</script></li><li class="js-percentile-work_65035698 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 65035698; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_65035698"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_65035698 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="65035698"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 65035698; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=65035698]").text(description); $(".js-view-count-work_65035698").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_65035698").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="65035698"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">15</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="14076" rel="nofollow" href="https://www.academia.edu/Documents/in/Transmission_Electron_Microscopy">Transmission Electron Microscopy</a>, <script data-card-contents-for-ri="14076" type="text/json">{"id":14076,"name":"Transmission Electron Microscopy","url":"https://www.academia.edu/Documents/in/Transmission_Electron_Microscopy?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="14079" rel="nofollow" href="https://www.academia.edu/Documents/in/Scanning_Transmission_Electron_Microscopy">Scanning Transmission Electron Microscopy</a>, <script data-card-contents-for-ri="14079" type="text/json">{"id":14079,"name":"Scanning Transmission Electron Microscopy","url":"https://www.academia.edu/Documents/in/Scanning_Transmission_Electron_Microscopy?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="46824" rel="nofollow" href="https://www.academia.edu/Documents/in/Echocardiography">Echocardiography</a><script data-card-contents-for-ri="46824" type="text/json">{"id":46824,"name":"Echocardiography","url":"https://www.academia.edu/Documents/in/Echocardiography?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=65035698]'), work: {"id":65035698,"title":"Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury","created_at":"2021-12-18T17:14:54.501-08:00","url":"https://www.academia.edu/65035698/Regular_and_moderate_exercise_before_experimental_sepsis_reduces_the_risk_of_lung_and_distal_organ_injury?f_ri=24731","dom_id":"work_65035698","summary":"Physical activity modulates inflammation and immune response in both normal and pathologic conditions. We investigated whether regular and moderate exercise before the induction of experimental sepsis reduces the risk of lung and distal organ injury and survival. One hundred twenty-four BALB/c mice were randomly assigned to two groups: sedentary (S) and trained (T). Animals in T group ran on a motorized treadmill, at moderate intensity, 5% grade, 30 min/day, 3 times a week for 8 wk. Cardiac adaptation to exercise was evaluated using echocardiography. Systolic volume and left ventricular mass were increased in T compared with S group. Both T and S groups were further randomized either to sepsis induced by cecal ligation and puncture surgery (CLP) or sham operation (control). After 24 h, lung mechanics and histology, the degree of cell apoptosis in lung, heart, kidney, liver, and small intestine villi, and interleukin (IL)-6, KC (IL-8 murine functional homolog), IL-1β, IL-10, and numb...","downloadable_attachments":[{"id":76796253,"asset_id":65035698,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":40789040,"first_name":"Nazareth","last_name":"Rocha","domain_name":"independent","page_name":"NazarethRocha","display_name":"Nazareth Rocha","profile_url":"https://independent.academia.edu/NazarethRocha?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":14076,"name":"Transmission Electron Microscopy","url":"https://www.academia.edu/Documents/in/Transmission_Electron_Microscopy?f_ri=24731","nofollow":true},{"id":14079,"name":"Scanning Transmission Electron Microscopy","url":"https://www.academia.edu/Documents/in/Scanning_Transmission_Electron_Microscopy?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":46824,"name":"Echocardiography","url":"https://www.academia.edu/Documents/in/Echocardiography?f_ri=24731","nofollow":true},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences?f_ri=24731"},{"id":55577,"name":"Survival","url":"https://www.academia.edu/Documents/in/Survival?f_ri=24731"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":96502,"name":"Applied","url":"https://www.academia.edu/Documents/in/Applied?f_ri=24731"},{"id":125076,"name":"Sepsis","url":"https://www.academia.edu/Documents/in/Sepsis?f_ri=24731"},{"id":162147,"name":"Applied Physiology","url":"https://www.academia.edu/Documents/in/Applied_Physiology?f_ri=24731"},{"id":182337,"name":"Acute Lung Injury","url":"https://www.academia.edu/Documents/in/Acute_Lung_Injury?f_ri=24731"},{"id":1348950,"name":"Respiratory Mechanics","url":"https://www.academia.edu/Documents/in/Respiratory_Mechanics?f_ri=24731"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin?f_ri=24731"},{"id":3589281,"name":"Ligation","url":"https://www.academia.edu/Documents/in/Ligation?f_ri=24731"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_62123687" data-work_id="62123687" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/62123687/Structure_activity_studies_on_therapeutic_potential_of_Thymoquinone_analogs_in_pancreatic_cancer">Structure-activity studies on therapeutic potential of Thymoquinone analogs in pancreatic cancer</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Purpose Pancreatic cancer (PC) is one of the deadliest of all tumors. Previously, we were the first to show that Thymoqui-none (TQ) derived from black seed (Nigella sativa) oil has anti-tumor activity against PC. However, the... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_62123687" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Purpose Pancreatic cancer (PC) is one of the deadliest of all tumors. Previously, we were the first to show that Thymoqui-none (TQ) derived from black seed (Nigella sativa) oil has anti-tumor activity against PC. However, the concentration of TQ required was ...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/62123687" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="d805f76f08f004b7d7f09d6844fe285e" rel="nofollow" data-download="{"attachment_id":74969598,"asset_id":62123687,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/74969598/download_file?st=MTczOTc5Mzg1MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="160682867" href="https://independent.academia.edu/padhyesubhash">subhash padhye</a><script data-card-contents-for-user="160682867" type="text/json">{"id":160682867,"first_name":"subhash","last_name":"padhye","domain_name":"independent","page_name":"padhyesubhash","display_name":"subhash padhye","profile_url":"https://independent.academia.edu/padhyesubhash?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_62123687 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="62123687"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 62123687, container: ".js-paper-rank-work_62123687", }); 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DNA lesions that have escaped DNA repair can induce replication stress and genomic breaks that induce... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_61916299" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Endogenous DNA damage is causally associated with the functional decline and transformation of stem cells that characterize ageing. DNA lesions that have escaped DNA repair can induce replication stress and genomic breaks that induce senescence and apoptosis. It is not clear how stem and proliferating cells cope with accumulating endogenous DNA lesions, and how these ultimately affect the physiology of cells and tissues. Here we have addressed these questions by investigating the hematopoietic system of mice deficient for Rev1, a core factor in DNA translesion synthesis (TLS), the post-replicative bypass of damaged nucleotides. Rev1 hematopoietic stem and progenitor cells displayed compromised proliferation, and replication stress that could be rescued with an antioxidant. The additional disruption of Xpc, essential for global-genome nucleotide excision repair (ggNER) of helix-distorting nucleotide lesions, resulted in the perinatal loss of hematopoietic stem cells, progressive loss...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/61916299" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="730ac5c8c53696d263cf893f1b95b4bf" rel="nofollow" data-download="{"attachment_id":74828131,"asset_id":61916299,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/74828131/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="45767226" href="https://independent.academia.edu/NielsWind">Niels Wind</a><script data-card-contents-for-user="45767226" type="text/json">{"id":45767226,"first_name":"Niels","last_name":"Wind","domain_name":"independent","page_name":"NielsWind","display_name":"Niels Wind","profile_url":"https://independent.academia.edu/NielsWind?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_61916299 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="61916299"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 61916299, container: ".js-paper-rank-work_61916299", }); 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repair","url":"https://www.academia.edu/Documents/in/DNA_repair?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":53113,"name":"Hematopoietic Stem Cells","url":"https://www.academia.edu/Documents/in/Hematopoietic_Stem_Cells?f_ri=24731"},{"id":60567,"name":"Cellular Senescence","url":"https://www.academia.edu/Documents/in/Cellular_Senescence?f_ri=24731"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":100732,"name":"Blood","url":"https://www.academia.edu/Documents/in/Blood?f_ri=24731"},{"id":159239,"name":"Bone marrow","url":"https://www.academia.edu/Documents/in/Bone_marrow?f_ri=24731"},{"id":176486,"name":"Genome","url":"https://www.academia.edu/Documents/in/Genome?f_ri=24731"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"},{"id":3789879,"name":"Cardiovascular medicine and haematology","url":"https://www.academia.edu/Documents/in/Cardiovascular_medicine_and_haematology?f_ri=24731"},{"id":3789883,"name":"Paediatrics and reproductive medicine","url":"https://www.academia.edu/Documents/in/Paediatrics_and_reproductive_medicine?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_57927672" data-work_id="57927672" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/57927672/Selective_Erasure_of_a_Fear_Memory">Selective Erasure of a Fear Memory</a></div></div><div class="u-pb4x u-mt3x"></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/57927672" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="27f05b2344c4209ca805feaf08b51260" rel="nofollow" data-download="{"attachment_id":72586685,"asset_id":57927672,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/72586685/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="51415175" href="https://independent.academia.edu/SJosselyn">Sheena Josselyn</a><script data-card-contents-for-user="51415175" type="text/json">{"id":51415175,"first_name":"Sheena","last_name":"Josselyn","domain_name":"independent","page_name":"SJosselyn","display_name":"Sheena Josselyn","profile_url":"https://independent.academia.edu/SJosselyn?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_57927672 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="57927672"><i class="u-m1x fa 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view-count u-mr2x" data-work-id="57927672"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 57927672; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=57927672]").text(description); $(".js-view-count-work_57927672").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_57927672").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="57927672"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">15</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="3931" rel="nofollow" href="https://www.academia.edu/Documents/in/Fear">Fear</a>, <script data-card-contents-for-ri="3931" type="text/json">{"id":3931,"name":"Fear","url":"https://www.academia.edu/Documents/in/Fear?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="6779" rel="nofollow" href="https://www.academia.edu/Documents/in/Science">Science</a>, <script data-card-contents-for-ri="6779" type="text/json">{"id":6779,"name":"Science","url":"https://www.academia.edu/Documents/in/Science?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="28235" rel="nofollow" href="https://www.academia.edu/Documents/in/Multidisciplinary">Multidisciplinary</a><script data-card-contents-for-ri="28235" type="text/json">{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=57927672]'), work: {"id":57927672,"title":"Selective Erasure of a Fear Memory","created_at":"2021-10-14T16:35:31.726-07:00","url":"https://www.academia.edu/57927672/Selective_Erasure_of_a_Fear_Memory?f_ri=24731","dom_id":"work_57927672","summary":null,"downloadable_attachments":[{"id":72586685,"asset_id":57927672,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":51415175,"first_name":"Sheena","last_name":"Josselyn","domain_name":"independent","page_name":"SJosselyn","display_name":"Sheena Josselyn","profile_url":"https://independent.academia.edu/SJosselyn?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":3931,"name":"Fear","url":"https://www.academia.edu/Documents/in/Fear?f_ri=24731","nofollow":true},{"id":6779,"name":"Science","url":"https://www.academia.edu/Documents/in/Science?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary?f_ri=24731","nofollow":true},{"id":37931,"name":"Transgenic Mice","url":"https://www.academia.edu/Documents/in/Transgenic_Mice?f_ri=24731"},{"id":43774,"name":"Learning","url":"https://www.academia.edu/Documents/in/Learning?f_ri=24731"},{"id":46858,"name":"Memory","url":"https://www.academia.edu/Documents/in/Memory?f_ri=24731"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":102041,"name":"Amnesia","url":"https://www.academia.edu/Documents/in/Amnesia?f_ri=24731"},{"id":142899,"name":"Thought","url":"https://www.academia.edu/Documents/in/Thought?f_ri=24731"},{"id":159962,"name":"Amygdala","url":"https://www.academia.edu/Documents/in/Amygdala?f_ri=24731"},{"id":501806,"name":"Protein Expression","url":"https://www.academia.edu/Documents/in/Protein_Expression?f_ri=24731"},{"id":1010725,"name":"Protein Binding","url":"https://www.academia.edu/Documents/in/Protein_Binding?f_ri=24731"},{"id":1944474,"name":"Diphtheria Toxin","url":"https://www.academia.edu/Documents/in/Diphtheria_Toxin?f_ri=24731"},{"id":2231834,"name":"Lateral Amygdala","url":"https://www.academia.edu/Documents/in/Lateral_Amygdala?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_56636000" data-work_id="56636000" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/56636000/Suppression_of_lung_metastases_by_the_CD26_DPP4_inhibitor_Vildagliptin_in_mice">Suppression of lung metastases by the CD26/DPP4 inhibitor Vildagliptin in mice</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Metastases rather than primary cancers determine nowadays the survival of patients. One of the most common primary malignancies is colorectal cancer and this type of tumor is characterized by a high tendency to spread metastases to the... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_56636000" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Metastases rather than primary cancers determine nowadays the survival of patients. One of the most common primary malignancies is colorectal cancer and this type of tumor is characterized by a high tendency to spread metastases to the lung and liver. CD26/DPP4 is a transmembrane molecule with enzymatic functions which cleaves biologically active peptides. Recently, CD26/DPP4 has become the focus of cancer research and it was shown that CD26/DPP4-positive cancer cells display increased metastatic activity. Here, we tested if the CD26/DPP4-inhibitor Vildagliptin suppresses the development and growth of mouse colorectal lung metastases. This inhibitor of CD26/DPP4 was employed on mouse (C57BL/6) colorectal lung metastases, established by intravenous injection of the syngeneic cell line MC38. For mechanistic analysis, a subcutaneous tumor model was used. The treatment with Vildagliptin significantly suppressed both, the incidence and growth of lung metastases. Autophagy markers (LC3, p62, and ATF4) decreased, apoptosis increased (TUNEL, pH3/Ki-76), and the cell cycle regulator pCDC2 was inhibited. In conclusion, we here showed an anti-tumor effect of Vildagliptin via downregulation of autophagy resulting in increased apoptosis and modulation of the cell cycle. We therefore propose Vildagliptin for the evaluation as a new therapeutic approach for the treatment of colorectal cancer lung metastases.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/56636000" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="386c65681c4d9fef8633f04bb44843d4" rel="nofollow" data-download="{"attachment_id":71925162,"asset_id":56636000,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/71925162/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="35353564" href="https://independent.academia.edu/IngridDemeester">Ingrid Demeester</a><script data-card-contents-for-user="35353564" type="text/json">{"id":35353564,"first_name":"Ingrid","last_name":"Demeester","domain_name":"independent","page_name":"IngridDemeester","display_name":"Ingrid Demeester","profile_url":"https://independent.academia.edu/IngridDemeester?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_56636000 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="56636000"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 56636000, container: ".js-paper-rank-work_56636000", }); });</script></li><li class="js-percentile-work_56636000 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 56636000; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_56636000"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_56636000 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="56636000"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 56636000; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=56636000]").text(description); $(".js-view-count-work_56636000").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_56636000").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="56636000"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">8</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="83906" rel="nofollow" href="https://www.academia.edu/Documents/in/Nitriles">Nitriles</a>, <script data-card-contents-for-ri="83906" type="text/json">{"id":83906,"name":"Nitriles","url":"https://www.academia.edu/Documents/in/Nitriles?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="84760" rel="nofollow" href="https://www.academia.edu/Documents/in/Mice">Mice</a>, <script data-card-contents-for-ri="84760" type="text/json">{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="244814" rel="nofollow" href="https://www.academia.edu/Documents/in/Clinical_Sciences">Clinical Sciences</a><script data-card-contents-for-ri="244814" type="text/json">{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=56636000]'), work: {"id":56636000,"title":"Suppression of lung metastases by the CD26/DPP4 inhibitor Vildagliptin in mice","created_at":"2021-10-08T12:53:43.471-07:00","url":"https://www.academia.edu/56636000/Suppression_of_lung_metastases_by_the_CD26_DPP4_inhibitor_Vildagliptin_in_mice?f_ri=24731","dom_id":"work_56636000","summary":"Metastases rather than primary cancers determine nowadays the survival of patients. One of the most common primary malignancies is colorectal cancer and this type of tumor is characterized by a high tendency to spread metastases to the lung and liver. CD26/DPP4 is a transmembrane molecule with enzymatic functions which cleaves biologically active peptides. Recently, CD26/DPP4 has become the focus of cancer research and it was shown that CD26/DPP4-positive cancer cells display increased metastatic activity. Here, we tested if the CD26/DPP4-inhibitor Vildagliptin suppresses the development and growth of mouse colorectal lung metastases. This inhibitor of CD26/DPP4 was employed on mouse (C57BL/6) colorectal lung metastases, established by intravenous injection of the syngeneic cell line MC38. For mechanistic analysis, a subcutaneous tumor model was used. The treatment with Vildagliptin significantly suppressed both, the incidence and growth of lung metastases. Autophagy markers (LC3, p62, and ATF4) decreased, apoptosis increased (TUNEL, pH3/Ki-76), and the cell cycle regulator pCDC2 was inhibited. In conclusion, we here showed an anti-tumor effect of Vildagliptin via downregulation of autophagy resulting in increased apoptosis and modulation of the cell cycle. We therefore propose Vildagliptin for the evaluation as a new therapeutic approach for the treatment of colorectal cancer lung metastases.","downloadable_attachments":[{"id":71925162,"asset_id":56636000,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":35353564,"first_name":"Ingrid","last_name":"Demeester","domain_name":"independent","page_name":"IngridDemeester","display_name":"Ingrid Demeester","profile_url":"https://independent.academia.edu/IngridDemeester?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":83906,"name":"Nitriles","url":"https://www.academia.edu/Documents/in/Nitriles?f_ri=24731","nofollow":true},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731","nofollow":true},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731","nofollow":true},{"id":1190805,"name":"Adamantane","url":"https://www.academia.edu/Documents/in/Adamantane?f_ri=24731"},{"id":1212103,"name":"Antineoplastic Agents","url":"https://www.academia.edu/Documents/in/Antineoplastic_Agents?f_ri=24731"},{"id":2440562,"name":"Colorectal Neoplasms","url":"https://www.academia.edu/Documents/in/Colorectal_Neoplasms?f_ri=24731"},{"id":3840853,"name":"lung neoplasms","url":"https://www.academia.edu/Documents/in/lung_neoplasms?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_53276550" data-work_id="53276550" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/53276550/Probiotics_Reduce_Bacterial_Colonization_and_Gastric_Inflammation_in_H_pylori_Infected_Mice">Probiotics Reduce Bacterial Colonization and Gastric Inflammation in H. pylori-Infected Mice</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Probiotics are characterized by their ability to interact with commensal microflora in the gastrointestinal tract to produce beneficial health effects. In vitro studies suggest that Lactobacillus species have the potential to suppress the... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_53276550" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Probiotics are characterized by their ability to interact with commensal microflora in the gastrointestinal tract to produce beneficial health effects. In vitro studies suggest that Lactobacillus species have the potential to suppress the growth of Helicobacter pylori. The goal of this study was to determine if pretreatment of mice with a commercial mixture of live probiotics (L. rhamnosus, strain R0011, and L. acidophilus, strain R0052) would suppress colonization of H. pylori, strain SS1. Thirty C57BL/6 female mice were divided into four groups: Group A was fed sterile water, group B received probiotics in sterile drinking water, group C was challenged orogastrically with H. pylori, and group D was pretreated with probiotics in drinking water prior to and following challenge with H. pylori. Rectal swabs, stomach homogenates, and luminal contents from ileum and colon were plated onto colistin nalidixic acid plates. Serial dilutions of stomach homogenates were plated onto H. pylori-sensitive agar plates and incubated under microaerophilic conditions. Tissue samples from the stomach were analyzed histologically to determine the degree of H. pylori colonization, mucosal inflammation, and epithelial cell apoptosis. Probiotics in drinking water did not affect the overall well-being of mice. Lactobacillus species were excreted in stools over the entire duration of treatment. Pretreatment with probiotics reduced the number of mice with H. pylori growth from stomach homgenates (100 to 50%; P = 0.02). The percentage of mice with moderate-severe H. pylori-induced inflammation in the gastric antrum was reduced with probiotic pretreatment (71 to 29%; P = 0.14). However, pretreatment with probiotics did not prevent H. pylori-induced apoptosis in the gastric mucosa. This preparation of probiotics provided a safe and novel approach for reducing H. pylori colonization and bacterial-induced inflammation of mice.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/53276550" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="dcabdd5ddb2e522c17ea1b9b79740a91" rel="nofollow" data-download="{"attachment_id":70189265,"asset_id":53276550,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/70189265/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="8665341" href="https://monash.academia.edu/DavidMitchell">David Mitchell</a><script data-card-contents-for-user="8665341" type="text/json">{"id":8665341,"first_name":"David","last_name":"Mitchell","domain_name":"monash","page_name":"DavidMitchell","display_name":"David Mitchell","profile_url":"https://monash.academia.edu/DavidMitchell?f_ri=24731","photo":"https://0.academia-photos.com/8665341/2881852/3366708/s65_david.mitchell.jpg"}</script></span></span></li><li class="js-paper-rank-work_53276550 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="53276550"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 53276550, container: ".js-paper-rank-work_53276550", }); });</script></li><li class="js-percentile-work_53276550 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 53276550; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_53276550"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_53276550 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="53276550"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 53276550; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=53276550]").text(description); $(".js-view-count-work_53276550").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_53276550").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="53276550"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">18</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="3274" rel="nofollow" href="https://www.academia.edu/Documents/in/Gastroenterology">Gastroenterology</a>, <script data-card-contents-for-ri="3274" type="text/json">{"id":3274,"name":"Gastroenterology","url":"https://www.academia.edu/Documents/in/Gastroenterology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="21460" rel="nofollow" href="https://www.academia.edu/Documents/in/Helicobacter_pylori">Helicobacter pylori</a>, <script data-card-contents-for-ri="21460" type="text/json">{"id":21460,"name":"Helicobacter pylori","url":"https://www.academia.edu/Documents/in/Helicobacter_pylori?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="48303" rel="nofollow" href="https://www.academia.edu/Documents/in/Colonization">Colonization</a><script data-card-contents-for-ri="48303" type="text/json">{"id":48303,"name":"Colonization","url":"https://www.academia.edu/Documents/in/Colonization?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=53276550]'), work: {"id":53276550,"title":"Probiotics Reduce Bacterial Colonization and Gastric Inflammation in H. pylori-Infected Mice","created_at":"2021-09-23T21:00:43.316-07:00","url":"https://www.academia.edu/53276550/Probiotics_Reduce_Bacterial_Colonization_and_Gastric_Inflammation_in_H_pylori_Infected_Mice?f_ri=24731","dom_id":"work_53276550","summary":"Probiotics are characterized by their ability to interact with commensal microflora in the gastrointestinal tract to produce beneficial health effects. In vitro studies suggest that Lactobacillus species have the potential to suppress the growth of Helicobacter pylori. The goal of this study was to determine if pretreatment of mice with a commercial mixture of live probiotics (L. rhamnosus, strain R0011, and L. acidophilus, strain R0052) would suppress colonization of H. pylori, strain SS1. Thirty C57BL/6 female mice were divided into four groups: Group A was fed sterile water, group B received probiotics in sterile drinking water, group C was challenged orogastrically with H. pylori, and group D was pretreated with probiotics in drinking water prior to and following challenge with H. pylori. Rectal swabs, stomach homogenates, and luminal contents from ileum and colon were plated onto colistin nalidixic acid plates. Serial dilutions of stomach homogenates were plated onto H. pylori-sensitive agar plates and incubated under microaerophilic conditions. Tissue samples from the stomach were analyzed histologically to determine the degree of H. pylori colonization, mucosal inflammation, and epithelial cell apoptosis. Probiotics in drinking water did not affect the overall well-being of mice. Lactobacillus species were excreted in stools over the entire duration of treatment. Pretreatment with probiotics reduced the number of mice with H. pylori growth from stomach homgenates (100 to 50%; P = 0.02). The percentage of mice with moderate-severe H. pylori-induced inflammation in the gastric antrum was reduced with probiotic pretreatment (71 to 29%; P = 0.14). However, pretreatment with probiotics did not prevent H. pylori-induced apoptosis in the gastric mucosa. This preparation of probiotics provided a safe and novel approach for reducing H. pylori colonization and bacterial-induced inflammation of mice.","downloadable_attachments":[{"id":70189265,"asset_id":53276550,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":8665341,"first_name":"David","last_name":"Mitchell","domain_name":"monash","page_name":"DavidMitchell","display_name":"David Mitchell","profile_url":"https://monash.academia.edu/DavidMitchell?f_ri=24731","photo":"https://0.academia-photos.com/8665341/2881852/3366708/s65_david.mitchell.jpg"}],"research_interests":[{"id":3274,"name":"Gastroenterology","url":"https://www.academia.edu/Documents/in/Gastroenterology?f_ri=24731","nofollow":true},{"id":21460,"name":"Helicobacter pylori","url":"https://www.academia.edu/Documents/in/Helicobacter_pylori?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":48303,"name":"Colonization","url":"https://www.academia.edu/Documents/in/Colonization?f_ri=24731","nofollow":true},{"id":79747,"name":"Colonisation","url":"https://www.academia.edu/Documents/in/Colonisation?f_ri=24731"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":106368,"name":"Lactobacillus","url":"https://www.academia.edu/Documents/in/Lactobacillus?f_ri=24731"},{"id":113903,"name":"Bacteria","url":"https://www.academia.edu/Documents/in/Bacteria?f_ri=24731"},{"id":120641,"name":"Drinking Water","url":"https://www.academia.edu/Documents/in/Drinking_Water?f_ri=24731"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731"},{"id":288801,"name":"Apoptose","url":"https://www.academia.edu/Documents/in/Apoptose?f_ri=24731"},{"id":537759,"name":"Gastrointestinal Tract","url":"https://www.academia.edu/Documents/in/Gastrointestinal_Tract?f_ri=24731"},{"id":780594,"name":"In Vitro Studies","url":"https://www.academia.edu/Documents/in/In_Vitro_Studies?f_ri=24731"},{"id":925054,"name":"Gastritis","url":"https://www.academia.edu/Documents/in/Gastritis?f_ri=24731"},{"id":997161,"name":"Health Effect","url":"https://www.academia.edu/Documents/in/Health_Effect?f_ri=24731"},{"id":1577787,"name":"H Pylori","url":"https://www.academia.edu/Documents/in/H_Pylori?f_ri=24731"},{"id":2061307,"name":"Nalidixic acid","url":"https://www.academia.edu/Documents/in/Nalidixic_acid?f_ri=24731"},{"id":2547982,"name":"Gastric mucosa","url":"https://www.academia.edu/Documents/in/Gastric_mucosa?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_50702923" data-work_id="50702923" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/50702923/Detection_of_virulent_Mareks_disease_virus_in_poultry_in_India">Detection of virulent Marek's disease virus in poultry in India</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Marek's disease virus (MDV) isolated from poultry flocks in three states of India was monitored for the virus occurrence in the field. The MDV genome was isolated from feather follicles, spleen, and liver of the chicken (173 samples).... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_50702923" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Marek's disease virus (MDV) isolated from poultry flocks in three states of India was monitored for the virus occurrence in the field. The MDV genome was isolated from feather follicles, spleen, and liver of the chicken (173 samples). Twenty two samples were positive for MDV genome in PCR and belonged to the serotype 1. The sequencing of MEQ gene of 11 samples revealed that nucleotide sequences of the isolate Ind-KA-01-06 was similar to the very virulent MDV, strain RB-1B. In situ hybridization studies also confirmed a presence of MDV serotype 1 in the infected liver tissues. Furthermore, the ability of the virus to induce apoptosis detected by flow cytometry showed that the virulent MDV induced apoptosis more efficiently than Turkey herpesvirus (HVT) vaccine virus. The present study showed the presence of virulent/very virulent MDV strains in the Indian poultry flocks.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/50702923" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="348b99435649e4ad04f67d1ac22e660f" rel="nofollow" data-download="{"attachment_id":68583878,"asset_id":50702923,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/68583878/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="5334368" href="https://independent.academia.edu/KumananKathaperumal">Kumanan Kathaperumal</a><script data-card-contents-for-user="5334368" type="text/json">{"id":5334368,"first_name":"Kumanan","last_name":"Kathaperumal","domain_name":"independent","page_name":"KumananKathaperumal","display_name":"Kumanan Kathaperumal","profile_url":"https://independent.academia.edu/KumananKathaperumal?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_50702923 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="50702923"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 50702923, container: ".js-paper-rank-work_50702923", }); });</script></li><li class="js-percentile-work_50702923 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 50702923; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_50702923"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_50702923 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="50702923"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 50702923; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=50702923]").text(description); $(".js-view-count-work_50702923").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_50702923").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="50702923"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">16</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="159" rel="nofollow" href="https://www.academia.edu/Documents/in/Microbiology">Microbiology</a>, <script data-card-contents-for-ri="159" type="text/json">{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="6599" rel="nofollow" href="https://www.academia.edu/Documents/in/Flow_Cytometry">Flow Cytometry</a>, <script data-card-contents-for-ri="6599" type="text/json">{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="6947" rel="nofollow" href="https://www.academia.edu/Documents/in/Medical_Microbiology">Medical Microbiology</a>, <script data-card-contents-for-ri="6947" type="text/json">{"id":6947,"name":"Medical Microbiology","url":"https://www.academia.edu/Documents/in/Medical_Microbiology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a><script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=50702923]'), work: {"id":50702923,"title":"Detection of virulent Marek's disease virus in poultry in India","created_at":"2021-08-03T23:57:56.715-07:00","url":"https://www.academia.edu/50702923/Detection_of_virulent_Mareks_disease_virus_in_poultry_in_India?f_ri=24731","dom_id":"work_50702923","summary":"Marek's disease virus (MDV) isolated from poultry flocks in three states of India was monitored for the virus occurrence in the field. The MDV genome was isolated from feather follicles, spleen, and liver of the chicken (173 samples). Twenty two samples were positive for MDV genome in PCR and belonged to the serotype 1. The sequencing of MEQ gene of 11 samples revealed that nucleotide sequences of the isolate Ind-KA-01-06 was similar to the very virulent MDV, strain RB-1B. In situ hybridization studies also confirmed a presence of MDV serotype 1 in the infected liver tissues. Furthermore, the ability of the virus to induce apoptosis detected by flow cytometry showed that the virulent MDV induced apoptosis more efficiently than Turkey herpesvirus (HVT) vaccine virus. The present study showed the presence of virulent/very virulent MDV strains in the Indian poultry flocks.","downloadable_attachments":[{"id":68583878,"asset_id":50702923,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":5334368,"first_name":"Kumanan","last_name":"Kathaperumal","domain_name":"independent","page_name":"KumananKathaperumal","display_name":"Kumanan Kathaperumal","profile_url":"https://independent.academia.edu/KumananKathaperumal?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology?f_ri=24731","nofollow":true},{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry?f_ri=24731","nofollow":true},{"id":6947,"name":"Medical Microbiology","url":"https://www.academia.edu/Documents/in/Medical_Microbiology?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":37836,"name":"In Situ Hybridization","url":"https://www.academia.edu/Documents/in/In_Situ_Hybridization?f_ri=24731"},{"id":43838,"name":"India","url":"https://www.academia.edu/Documents/in/India?f_ri=24731"},{"id":49018,"name":"Spleen","url":"https://www.academia.edu/Documents/in/Spleen?f_ri=24731"},{"id":52873,"name":"Virulence","url":"https://www.academia.edu/Documents/in/Virulence?f_ri=24731"},{"id":71437,"name":"Liver","url":"https://www.academia.edu/Documents/in/Liver?f_ri=24731"},{"id":118339,"name":"Polymerase Chain Reaction","url":"https://www.academia.edu/Documents/in/Polymerase_Chain_Reaction?f_ri=24731"},{"id":132052,"name":"Marek Disease","url":"https://www.academia.edu/Documents/in/Marek_Disease?f_ri=24731"},{"id":366620,"name":"POULTRY DISEASES","url":"https://www.academia.edu/Documents/in/POULTRY_DISEASES?f_ri=24731"},{"id":402759,"name":"Chickens","url":"https://www.academia.edu/Documents/in/Chickens?f_ri=24731"},{"id":430462,"name":"Feathers","url":"https://www.academia.edu/Documents/in/Feathers?f_ri=24731"},{"id":2032368,"name":"Serotyping","url":"https://www.academia.edu/Documents/in/Serotyping?f_ri=24731"},{"id":3675689,"name":"Chick embryo","url":"https://www.academia.edu/Documents/in/Chick_embryo?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_49700080 coauthored" data-work_id="49700080" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/49700080/Preclinical_Studies_of_TW_37_a_New_Nonpeptidic_Small_Molecule_Inhibitor_of_Bcl_2_in_Diffuse_Large_Cell_Lymphoma_Xenograft_Model_Reveal_Drug_Action_on_Both_Bcl_2_and_Mcl_1">Preclinical Studies of TW-37, a New Nonpeptidic Small-Molecule Inhibitor of Bcl-2, in Diffuse Large Cell Lymphoma Xenograft Model Reveal Drug Action on Both Bcl-2 and Mcl-1</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Overexpression of Bcl-2 protein has been observed in more than 80% of B-cell lymphomas, including diffuse large cell lymphoma (DLCL), the most common subtype of non-Hodgkin's lymphoma. We have previously employed the natural product... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_49700080" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Overexpression of Bcl-2 protein has been observed in more than 80% of B-cell lymphomas, including diffuse large cell lymphoma (DLCL), the most common subtype of non-Hodgkin's lymphoma. We have previously employed the natural product (À)-gossypol to test its therapeutic potential as a small-molecule inhibitor of Bcl-2 for the treatment of B-cell lymphomas. Experimental Design: Recently, we have used a structure-based strategy to design a new class of potent small-molecule inhibitor acting on Bcl-2. One such lead compound is the benzenesulfonyl derivative TW-37, which was designed to target the BH3-binding groove in Bcl-2 where proapoptotic Bcl-2 proteins, such as Bak, Bax, Bid, and Bim bind. Results: In our fluorescence polarization^based binding assays using recombinant Bcl-2, Bcl-X L , and Mcl-1proteins,TW-37 binds to Bcl-2, Bcl-X L , and Mcl-1with K i values of 290, 1,110 and 260 nmol/L, respectively. Hence,TW-37 is a potent inhibitor of Bcl-2 and has >3-fold selectivity over Bcl-X L. In vitro,TW-37 showed significant antiproliferative effect in a de novo chemoresistant WSU-DLCL 2 lymphoma cell line and primary cells obtained from a lymphoma patient with no effect on normal peripheral blood lymphocytes. Coimmunoprecipitation experiments showed that TW-37 disrupted heterodimer formation between Bax or truncated-Bid and antiapoptotic proteins in the order Mcl-1 > Bcl-2 >> Bcl-X L. As expected, TW-37 caused apoptotic death. Pre-exposure of lymphoma cells toTW-37 significantly enhanced the killing effect of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) regimen. The maximum tolerated dose of TW-37 in severe combined immunodeficient (SCID) mice was 40 mg/kg for three i.v. injections when given alone and 20 mg/kg, Â3 when given in combination with CHOP. UsingWSU-DLCL 2-SCID mouse xenograft model, the addition of TW-37 to CHOP resulted in more complete tumor inhibition compared with either CHOP orTW-37 alone. Conclusions: We conclude that the administration of TW-37, as a potent Bcl-2 and Mcl-1inhibitor, to standard chemotherapy may prove an effective strategy in the treatment of B-celllymphoma.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/49700080" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="d2dbd530016abdf2fe4de64f523c0751" rel="nofollow" data-download="{"attachment_id":67974994,"asset_id":49700080,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/67974994/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="213932770" href="https://independent.academia.edu/BenChen99">Ben Chen</a><script data-card-contents-for-user="213932770" type="text/json">{"id":213932770,"first_name":"Ben","last_name":"Chen","domain_name":"independent","page_name":"BenChen99","display_name":"Ben Chen","profile_url":"https://independent.academia.edu/BenChen99?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-49700080">+1</span><div class="hidden js-additional-users-49700080"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://wayne.academia.edu/Goustin">Anton-Scott Goustin</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-49700080'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-49700080').html(); 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We have previously employed the natural product (À)-gossypol to test its therapeutic potential as a small-molecule inhibitor of Bcl-2 for the treatment of B-cell lymphomas. Experimental Design: Recently, we have used a structure-based strategy to design a new class of potent small-molecule inhibitor acting on Bcl-2. One such lead compound is the benzenesulfonyl derivative TW-37, which was designed to target the BH3-binding groove in Bcl-2 where proapoptotic Bcl-2 proteins, such as Bak, Bax, Bid, and Bim bind. Results: In our fluorescence polarization^based binding assays using recombinant Bcl-2, Bcl-X L , and Mcl-1proteins,TW-37 binds to Bcl-2, Bcl-X L , and Mcl-1with K i values of 290, 1,110 and 260 nmol/L, respectively. Hence,TW-37 is a potent inhibitor of Bcl-2 and has \u003e3-fold selectivity over Bcl-X L. In vitro,TW-37 showed significant antiproliferative effect in a de novo chemoresistant WSU-DLCL 2 lymphoma cell line and primary cells obtained from a lymphoma patient with no effect on normal peripheral blood lymphocytes. Coimmunoprecipitation experiments showed that TW-37 disrupted heterodimer formation between Bax or truncated-Bid and antiapoptotic proteins in the order Mcl-1 \u003e Bcl-2 \u003e\u003e Bcl-X L. As expected, TW-37 caused apoptotic death. Pre-exposure of lymphoma cells toTW-37 significantly enhanced the killing effect of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) regimen. The maximum tolerated dose of TW-37 in severe combined immunodeficient (SCID) mice was 40 mg/kg for three i.v. injections when given alone and 20 mg/kg, Â3 when given in combination with CHOP. UsingWSU-DLCL 2-SCID mouse xenograft model, the addition of TW-37 to CHOP resulted in more complete tumor inhibition compared with either CHOP orTW-37 alone. Conclusions: We conclude that the administration of TW-37, as a potent Bcl-2 and Mcl-1inhibitor, to standard chemotherapy may prove an effective strategy in the treatment of B-celllymphoma.","downloadable_attachments":[{"id":67974994,"asset_id":49700080,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":213932770,"first_name":"Ben","last_name":"Chen","domain_name":"independent","page_name":"BenChen99","display_name":"Ben Chen","profile_url":"https://independent.academia.edu/BenChen99?f_ri=24731","photo":"/images/s65_no_pic.png"},{"id":42149560,"first_name":"Anton-Scott","last_name":"Goustin","domain_name":"wayne","page_name":"Goustin","display_name":"Anton-Scott Goustin","profile_url":"https://wayne.academia.edu/Goustin?f_ri=24731","photo":"https://0.academia-photos.com/42149560/15421768/16049539/s65_anton-scott.goustin.jpg"}],"research_interests":[{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":37834,"name":"Western blotting","url":"https://www.academia.edu/Documents/in/Western_blotting?f_ri=24731","nofollow":true},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731","nofollow":true},{"id":216699,"name":"Immunoprecipitation","url":"https://www.academia.edu/Documents/in/Immunoprecipitation?f_ri=24731"},{"id":314240,"name":"Doxorubicin","url":"https://www.academia.edu/Documents/in/Doxorubicin?f_ri=24731"},{"id":394389,"name":"Small Molecule","url":"https://www.academia.edu/Documents/in/Small_Molecule?f_ri=24731"},{"id":541328,"name":"Diffuse Large B-Cell Lymphoma","url":"https://www.academia.edu/Documents/in/Diffuse_Large_B-Cell_Lymphoma?f_ri=24731"},{"id":1010725,"name":"Protein Binding","url":"https://www.academia.edu/Documents/in/Protein_Binding?f_ri=24731"},{"id":1198588,"name":"Cyclophosphamide","url":"https://www.academia.edu/Documents/in/Cyclophosphamide?f_ri=24731"},{"id":1212103,"name":"Antineoplastic Agents","url":"https://www.academia.edu/Documents/in/Antineoplastic_Agents?f_ri=24731"},{"id":1524090,"name":"Benzamides","url":"https://www.academia.edu/Documents/in/Benzamides?f_ri=24731"},{"id":3200262,"name":"Diffuse large B cell lymphoma","url":"https://www.academia.edu/Documents/in/Diffuse_large_B_cell_lymphoma?f_ri=24731"},{"id":3448420,"name":"Vincristine","url":"https://www.academia.edu/Documents/in/Vincristine?f_ri=24731"},{"id":3483787,"name":"Prednisone","url":"https://www.academia.edu/Documents/in/Prednisone?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_1618799" data-work_id="1618799" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/1618799/Physicochemical_and_biological_characterization_of_1E10_Anti_Idiotype_vaccine">Physicochemical and biological characterization of 1E10 Anti-Idiotype vaccine</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Background: 1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH) 3 , in several clinical trials for... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_1618799" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Background: 1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH) 3 , in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/1618799" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="e0bc2e2edba3a2047c51fe694abe3ba4" rel="nofollow" data-download="{"attachment_id":30996688,"asset_id":1618799,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/30996688/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="999193" href="https://sld.academia.edu/AdolfoCastillo">Adolfo Castillo</a><script data-card-contents-for-user="999193" type="text/json">{"id":999193,"first_name":"Adolfo","last_name":"Castillo","domain_name":"sld","page_name":"AdolfoCastillo","display_name":"Adolfo Castillo","profile_url":"https://sld.academia.edu/AdolfoCastillo?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_1618799 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="1618799"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 1618799, container: ".js-paper-rank-work_1618799", }); 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This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH) 3 , in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method.","downloadable_attachments":[{"id":30996688,"asset_id":1618799,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":999193,"first_name":"Adolfo","last_name":"Castillo","domain_name":"sld","page_name":"AdolfoCastillo","display_name":"Adolfo Castillo","profile_url":"https://sld.academia.edu/AdolfoCastillo?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":48,"name":"Engineering","url":"https://www.academia.edu/Documents/in/Engineering?f_ri=24731","nofollow":true},{"id":522,"name":"Thermodynamics","url":"https://www.academia.edu/Documents/in/Thermodynamics?f_ri=24731","nofollow":true},{"id":531,"name":"Organic Chemistry","url":"https://www.academia.edu/Documents/in/Organic_Chemistry?f_ri=24731","nofollow":true},{"id":532,"name":"Physical 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Growth","url":"https://www.academia.edu/Documents/in/Tumor_Growth?f_ri=24731"},{"id":1198588,"name":"Cyclophosphamide","url":"https://www.academia.edu/Documents/in/Cyclophosphamide?f_ri=24731"},{"id":1256747,"name":"Oxidation-Reduction","url":"https://www.academia.edu/Documents/in/Oxidation-Reduction?f_ri=24731"},{"id":1266470,"name":"Polyethylenimine","url":"https://www.academia.edu/Documents/in/Polyethylenimine?f_ri=24731"},{"id":1272890,"name":"Electric Impedance","url":"https://www.academia.edu/Documents/in/Electric_Impedance?f_ri=24731"},{"id":1417547,"name":"Ceramides","url":"https://www.academia.edu/Documents/in/Ceramides?f_ri=24731"},{"id":1434630,"name":"Polyethylene Glycols","url":"https://www.academia.edu/Documents/in/Polyethylene_Glycols?f_ri=24731"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology?f_ri=24731"},{"id":1703031,"name":"Mannitol","url":"https://www.academia.edu/Documents/in/Mannitol?f_ri=24731"},{"id":1900203,"name":"Hemolysis","url":"https://www.academia.edu/Documents/in/Hemolysis?f_ri=24731"},{"id":2187010,"name":"Molecular Pharmaceutics","url":"https://www.academia.edu/Documents/in/Molecular_Pharmaceutics?f_ri=24731"},{"id":2467566,"name":"Molecular Sequence Data","url":"https://www.academia.edu/Documents/in/Molecular_Sequence_Data?f_ri=24731"},{"id":2533047,"name":"fibroblasts","url":"https://www.academia.edu/Documents/in/fibroblasts?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_29951335" data-work_id="29951335" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/29951335/The_appearances_of_autolytic_and_apoptotic_markers_are_concomitant_but_differently_regulated_in_carbon_starving_Aspergillus_nidulans_cultures">The appearances of autolytic and apoptotic markers are concomitant but differently regulated in carbon-starving Aspergillus nidulans cultures</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">In ageing, carbon-depleted cultures of Aspergillus nidulans strain FGSC 26 progressing apoptotic-type cell death was detected, characterised by increasing numbers of Annexin V and TUNEL stained cells after protoplastation. DAPI staining... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_29951335" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">In ageing, carbon-depleted cultures of Aspergillus nidulans strain FGSC 26 progressing apoptotic-type cell death was detected, characterised by increasing numbers of Annexin V and TUNEL stained cells after protoplastation. DAPI staining of autolysing mycelia revealed numerous nuclei with elongated, stick-like morphology, which was not observed in surviving hyphal fragments representing a cell population adapted to carbon starvation. Apoptotic cell death was also progressing in aging cultures of the nonautolysing loss-of-function fluG and DbrlA mutants, indicating that apoptotic cell death and autolysis were regulated independently. In accordance with this, sphingosine derivatives added to A. nidulans cultures increased cell death rates without influencing autolytic biomass losses and hydrolase production.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/29951335" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="ed0ecdddeb919bb9a0f9b5d6bfd7e77c" rel="nofollow" data-download="{"attachment_id":50409223,"asset_id":29951335,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/50409223/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="36143105" href="https://independent.academia.edu/Istv%C3%A1nP%C3%B3csi">István Pócsi</a><script data-card-contents-for-user="36143105" type="text/json">{"id":36143105,"first_name":"István","last_name":"Pócsi","domain_name":"independent","page_name":"IstvánPócsi","display_name":"István Pócsi","profile_url":"https://independent.academia.edu/Istv%C3%A1nP%C3%B3csi?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_29951335 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="29951335"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 29951335, container: ".js-paper-rank-work_29951335", }); 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$(".js-view-count[data-work-id=29951335]").text(description); $(".js-view-count-work_29951335").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_29951335").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="29951335"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">6</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="23323" rel="nofollow" href="https://www.academia.edu/Documents/in/Transcription_Factors">Transcription Factors</a>, <script data-card-contents-for-ri="23323" type="text/json">{"id":23323,"name":"Transcription Factors","url":"https://www.academia.edu/Documents/in/Transcription_Factors?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="47884" rel="nofollow" href="https://www.academia.edu/Documents/in/Biological_Sciences">Biological Sciences</a>, <script data-card-contents-for-ri="47884" type="text/json">{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="112576" rel="nofollow" href="https://www.academia.edu/Documents/in/Cell_Death">Cell Death</a><script data-card-contents-for-ri="112576" type="text/json">{"id":112576,"name":"Cell Death","url":"https://www.academia.edu/Documents/in/Cell_Death?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=29951335]'), work: {"id":29951335,"title":"The appearances of autolytic and apoptotic markers are concomitant but differently regulated in carbon-starving Aspergillus nidulans cultures","created_at":"2016-11-18T20:42:07.951-08:00","url":"https://www.academia.edu/29951335/The_appearances_of_autolytic_and_apoptotic_markers_are_concomitant_but_differently_regulated_in_carbon_starving_Aspergillus_nidulans_cultures?f_ri=24731","dom_id":"work_29951335","summary":"In ageing, carbon-depleted cultures of Aspergillus nidulans strain FGSC 26 progressing apoptotic-type cell death was detected, characterised by increasing numbers of Annexin V and TUNEL stained cells after protoplastation. DAPI staining of autolysing mycelia revealed numerous nuclei with elongated, stick-like morphology, which was not observed in surviving hyphal fragments representing a cell population adapted to carbon starvation. Apoptotic cell death was also progressing in aging cultures of the nonautolysing loss-of-function fluG and DbrlA mutants, indicating that apoptotic cell death and autolysis were regulated independently. In accordance with this, sphingosine derivatives added to A. nidulans cultures increased cell death rates without influencing autolytic biomass losses and hydrolase production.","downloadable_attachments":[{"id":50409223,"asset_id":29951335,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":36143105,"first_name":"István","last_name":"Pócsi","domain_name":"independent","page_name":"IstvánPócsi","display_name":"István Pócsi","profile_url":"https://independent.academia.edu/Istv%C3%A1nP%C3%B3csi?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":23323,"name":"Transcription Factors","url":"https://www.academia.edu/Documents/in/Transcription_Factors?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences?f_ri=24731","nofollow":true},{"id":112576,"name":"Cell Death","url":"https://www.academia.edu/Documents/in/Cell_Death?f_ri=24731","nofollow":true},{"id":289467,"name":"Aspergillus Nidulans","url":"https://www.academia.edu/Documents/in/Aspergillus_Nidulans?f_ri=24731"},{"id":1884612,"name":"Autolysis","url":"https://www.academia.edu/Documents/in/Autolysis?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_29643167" data-work_id="29643167" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/29643167/Decreased_phagocytosis_of_apoptotic_cells_in_diseased_SLE_mice">Decreased phagocytosis of apoptotic cells in diseased SLE mice</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Antibodies against nucleosomes are a serological hallmark of systemic lupus erythematosus (SLE). Apoptotic cells are the unique source of nucleosomes, which are formed through cleavage of chromatin by nucleases. These nucleosomes and... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_29643167" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Antibodies against nucleosomes are a serological hallmark of systemic lupus erythematosus (SLE). Apoptotic cells are the unique source of nucleosomes, which are formed through cleavage of chromatin by nucleases. These nucleosomes and other autoantigens targeted in SLE are expressed in apoptotic blebs or at the surface of apoptotic cells. Therefore, it is conceivable that circulating antibodies can influence apoptotic cell clearance. Using an in vitro phagocytosis assay, we analysed the phagocytic efficacy for apoptotic cells of resident peritoneal macrophages from pre-morbid and diseased lupus mice. The assay was carried out in the presence of autologous serum, using autologous apoptotic thymocytes as targets. Under these conditions macrophages from diseased MRL/lpr and NZB NZW(F1) lupus mice, and from age-matched NZB mice showed a decreased phagocytic efficacy (decrease 47%, 48% and 37%, respectively compared to measurements in pre-morbid mice). The cause of this decrease resides in the serum, and is not due to an acquired defect of macrophages. In conclusion, during disease progression in murine SLE, apoptotic cell clearance becomes impaired, which might amplify further disease progression.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/29643167" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="c92c25b5ec9eb37f6291de52a6965990" rel="nofollow" data-download="{"attachment_id":50080576,"asset_id":29643167,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/50080576/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="46496846" href="https://radboudumc.academia.edu/JoBerden">Jo Berden</a><script data-card-contents-for-user="46496846" type="text/json">{"id":46496846,"first_name":"Jo","last_name":"Berden","domain_name":"radboudumc","page_name":"JoBerden","display_name":"Jo Berden","profile_url":"https://radboudumc.academia.edu/JoBerden?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_29643167 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="29643167"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 29643167, container: ".js-paper-rank-work_29643167", }); 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$(".js-view-count[data-work-id=29643167]").text(description); $(".js-view-count-work_29643167").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_29643167").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="29643167"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">10</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="1290" rel="nofollow" href="https://www.academia.edu/Documents/in/Immunology">Immunology</a>, <script data-card-contents-for-ri="1290" type="text/json">{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="12320" rel="nofollow" href="https://www.academia.edu/Documents/in/Autoimmunity">Autoimmunity</a>, <script data-card-contents-for-ri="12320" type="text/json">{"id":12320,"name":"Autoimmunity","url":"https://www.academia.edu/Documents/in/Autoimmunity?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="66614" rel="nofollow" href="https://www.academia.edu/Documents/in/Systemic_Lupus_Erythematosus">Systemic Lupus Erythematosus</a><script data-card-contents-for-ri="66614" type="text/json">{"id":66614,"name":"Systemic Lupus Erythematosus","url":"https://www.academia.edu/Documents/in/Systemic_Lupus_Erythematosus?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=29643167]'), work: {"id":29643167,"title":"Decreased phagocytosis of apoptotic cells in diseased SLE mice","created_at":"2016-11-03T07:43:33.191-07:00","url":"https://www.academia.edu/29643167/Decreased_phagocytosis_of_apoptotic_cells_in_diseased_SLE_mice?f_ri=24731","dom_id":"work_29643167","summary":"Antibodies against nucleosomes are a serological hallmark of systemic lupus erythematosus (SLE). Apoptotic cells are the unique source of nucleosomes, which are formed through cleavage of chromatin by nucleases. These nucleosomes and other autoantigens targeted in SLE are expressed in apoptotic blebs or at the surface of apoptotic cells. Therefore, it is conceivable that circulating antibodies can influence apoptotic cell clearance. Using an in vitro phagocytosis assay, we analysed the phagocytic efficacy for apoptotic cells of resident peritoneal macrophages from pre-morbid and diseased lupus mice. The assay was carried out in the presence of autologous serum, using autologous apoptotic thymocytes as targets. Under these conditions macrophages from diseased MRL/lpr and NZB NZW(F1) lupus mice, and from age-matched NZB mice showed a decreased phagocytic efficacy (decrease 47%, 48% and 37%, respectively compared to measurements in pre-morbid mice). The cause of this decrease resides in the serum, and is not due to an acquired defect of macrophages. In conclusion, during disease progression in murine SLE, apoptotic cell clearance becomes impaired, which might amplify further disease progression.","downloadable_attachments":[{"id":50080576,"asset_id":29643167,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":46496846,"first_name":"Jo","last_name":"Berden","domain_name":"radboudumc","page_name":"JoBerden","display_name":"Jo Berden","profile_url":"https://radboudumc.academia.edu/JoBerden?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology?f_ri=24731","nofollow":true},{"id":12320,"name":"Autoimmunity","url":"https://www.academia.edu/Documents/in/Autoimmunity?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":66614,"name":"Systemic Lupus Erythematosus","url":"https://www.academia.edu/Documents/in/Systemic_Lupus_Erythematosus?f_ri=24731","nofollow":true},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":211309,"name":"Nucleosomes","url":"https://www.academia.edu/Documents/in/Nucleosomes?f_ri=24731"},{"id":280237,"name":"T lymphocytes","url":"https://www.academia.edu/Documents/in/T_lymphocytes?f_ri=24731"},{"id":376644,"name":"Phagocytosis","url":"https://www.academia.edu/Documents/in/Phagocytosis?f_ri=24731"},{"id":546419,"name":"Age Factors","url":"https://www.academia.edu/Documents/in/Age_Factors?f_ri=24731"},{"id":584615,"name":"Disease Progression","url":"https://www.academia.edu/Documents/in/Disease_Progression?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_4197492" data-work_id="4197492" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/4197492/Central_effects_of_rat_versus_mouse_leptin_ingestive_behavior_and_adipose_apoptosis">Central effects of rat versus mouse leptin: ingestive behavior and adipose apoptosis</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Leptin decreases food intake, body weight and fat mass while sparing lean mass. Although mouse leptin (ML) and rat leptin (RL) are 95.9% identical, our impression from previous studies was that they were not equally potent in rats. Thus,... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_4197492" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Leptin decreases food intake, body weight and fat mass while sparing lean mass. Although mouse leptin (ML) and rat leptin (RL) are 95.9% identical, our impression from previous studies was that they were not equally potent in rats. Thus, in the present study, 0 g (vehicle) or 10 g of ML or RL was injected into the lateral ventricle of rats (eight per treatment) once a day for four consecutive days. Body temperature, body weight, food intake and water intake were measured daily. Intrascapular and perirenal brown fat pads, white fat tissues (retroperitoneal, epididymal and inguinal fat pads) and the gastrocnemius muscle were collected and weighed 24 h after the last treatments. Body temperature was not affected by either ML or RL. Both ML and RL caused significant reductions in food intake (P < 0.05), and there was no difference between them. ML and RL also similarly inhibited water intake on days 2 and 3 (P < 0.05). By day 5 both ML-and RL-treated rats had lost weight (11.6 and 15.4 g, respectively), while vehicle-treated rats gained weight (6.8 g). Weights of retroperitoneal and epididymal fat pads, but not other tissues, were reduced similarly by both leptin treatments (P < 0.05). However, an increased apoptotic response was detected in the retroperitoneal fat tissue of RL-but not ML-treated rats (P < 0.05). These results suggest that RL is more effective than ML in inducing apoptosis in retroperitoneal fat tissue after i.c.v. injection in rats.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/4197492" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="c2b3ecfe7fecbe50db1012210e09f934" rel="nofollow" data-download="{"attachment_id":49990204,"asset_id":4197492,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/49990204/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="5078224" href="https://uga.academia.edu/MaryAnneDellaFera">MaryAnne DellaFera</a><script data-card-contents-for-user="5078224" type="text/json">{"id":5078224,"first_name":"MaryAnne","last_name":"DellaFera","domain_name":"uga","page_name":"MaryAnneDellaFera","display_name":"MaryAnne DellaFera","profile_url":"https://uga.academia.edu/MaryAnneDellaFera?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_4197492 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="4197492"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 4197492, container: ".js-paper-rank-work_4197492", }); });</script></li><li class="js-percentile-work_4197492 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 4197492; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_4197492"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_4197492 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="4197492"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 4197492; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=4197492]").text(description); $(".js-view-count-work_4197492").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_4197492").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="4197492"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">16</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="4228" rel="nofollow" href="https://www.academia.edu/Documents/in/Skeletal_muscle_biology">Skeletal muscle biology</a>, <script data-card-contents-for-ri="4228" type="text/json">{"id":4228,"name":"Skeletal muscle biology","url":"https://www.academia.edu/Documents/in/Skeletal_muscle_biology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="29980" rel="nofollow" href="https://www.academia.edu/Documents/in/Animal_Production">Animal Production</a>, <script data-card-contents-for-ri="29980" type="text/json">{"id":29980,"name":"Animal Production","url":"https://www.academia.edu/Documents/in/Animal_Production?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="52489" rel="nofollow" href="https://www.academia.edu/Documents/in/Adipose_tissue">Adipose tissue</a><script data-card-contents-for-ri="52489" type="text/json">{"id":52489,"name":"Adipose tissue","url":"https://www.academia.edu/Documents/in/Adipose_tissue?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=4197492]'), work: {"id":4197492,"title":"Central effects of rat versus mouse leptin: ingestive behavior and adipose apoptosis","created_at":"2013-08-08T02:39:43.717-07:00","url":"https://www.academia.edu/4197492/Central_effects_of_rat_versus_mouse_leptin_ingestive_behavior_and_adipose_apoptosis?f_ri=24731","dom_id":"work_4197492","summary":"Leptin decreases food intake, body weight and fat mass while sparing lean mass. Although mouse leptin (ML) and rat leptin (RL) are 95.9% identical, our impression from previous studies was that they were not equally potent in rats. Thus, in the present study, 0 g (vehicle) or 10 g of ML or RL was injected into the lateral ventricle of rats (eight per treatment) once a day for four consecutive days. Body temperature, body weight, food intake and water intake were measured daily. Intrascapular and perirenal brown fat pads, white fat tissues (retroperitoneal, epididymal and inguinal fat pads) and the gastrocnemius muscle were collected and weighed 24 h after the last treatments. Body temperature was not affected by either ML or RL. Both ML and RL caused significant reductions in food intake (P \u003c 0.05), and there was no difference between them. ML and RL also similarly inhibited water intake on days 2 and 3 (P \u003c 0.05). By day 5 both ML-and RL-treated rats had lost weight (11.6 and 15.4 g, respectively), while vehicle-treated rats gained weight (6.8 g). Weights of retroperitoneal and epididymal fat pads, but not other tissues, were reduced similarly by both leptin treatments (P \u003c 0.05). However, an increased apoptotic response was detected in the retroperitoneal fat tissue of RL-but not ML-treated rats (P \u003c 0.05). These results suggest that RL is more effective than ML in inducing apoptosis in retroperitoneal fat tissue after i.c.v. injection in rats.","downloadable_attachments":[{"id":49990204,"asset_id":4197492,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":5078224,"first_name":"MaryAnne","last_name":"DellaFera","domain_name":"uga","page_name":"MaryAnneDellaFera","display_name":"MaryAnne DellaFera","profile_url":"https://uga.academia.edu/MaryAnneDellaFera?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":4228,"name":"Skeletal muscle biology","url":"https://www.academia.edu/Documents/in/Skeletal_muscle_biology?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":29980,"name":"Animal Production","url":"https://www.academia.edu/Documents/in/Animal_Production?f_ri=24731","nofollow":true},{"id":52489,"name":"Adipose tissue","url":"https://www.academia.edu/Documents/in/Adipose_tissue?f_ri=24731","nofollow":true},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731"},{"id":135357,"name":"Leptin","url":"https://www.academia.edu/Documents/in/Leptin?f_ri=24731"},{"id":218820,"name":"Eating","url":"https://www.academia.edu/Documents/in/Eating?f_ri=24731"},{"id":240716,"name":"Body Temperature","url":"https://www.academia.edu/Documents/in/Body_Temperature?f_ri=24731"},{"id":241044,"name":"Food intake","url":"https://www.academia.edu/Documents/in/Food_intake?f_ri=24731"},{"id":353163,"name":"Fat Mass","url":"https://www.academia.edu/Documents/in/Fat_Mass?f_ri=24731"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats?f_ri=24731"},{"id":413194,"name":"Analysis of Variance","url":"https://www.academia.edu/Documents/in/Analysis_of_Variance?f_ri=24731"},{"id":472784,"name":"Adipocytes","url":"https://www.academia.edu/Documents/in/Adipocytes?f_ri=24731"},{"id":564878,"name":"Body Weight","url":"https://www.academia.edu/Documents/in/Body_Weight?f_ri=24731"},{"id":644860,"name":"Veterinary Sciences","url":"https://www.academia.edu/Documents/in/Veterinary_Sciences?f_ri=24731"},{"id":1735620,"name":"Water intake","url":"https://www.academia.edu/Documents/in/Water_intake?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_4217920" data-work_id="4217920" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/4217920/Mechanisms_of_neural_cell_death_Implications_for_development_of_neuroprotective_treatment_strategies">Mechanisms of neural cell death: Implications for development of neuroprotective treatment strategies</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">It has been increasingly recognized that cell death phenotypes and their molecular mechanisms are highly diverse. Necrosis is no longer considered a single entity, passively mediated by energy failure. Moreover, caspase-dependent... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_4217920" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">It has been increasingly recognized that cell death phenotypes and their molecular mechanisms are highly diverse. Necrosis is no longer considered a single entity, passively mediated by energy failure. Moreover, caspase-dependent apoptosis is not the only pathway involved in programmed cell death or even the only apoptotic mechanism. Recent experimental work emphasizes the diverse and interrelated nature of cell death mechanisms. Thus, there are both caspase-dependent and caspase-independent forms of apoptosis, which may differ morphologically as well as mechanistically. There are also necrotic-like phenotypes that requirede novo protein synthesis and are, therefore, forms of programmed cell death. In addition, forms of cell death showing certain morphological features of both necrosis and apoptosis have been identified, leading to the term aponecrosis. Considerable experimental evidence also shows that modulation of one form of cell death may lead to another. Together, these observations underscore the need to substantially revise our conceptions about neuroprotection strategies. Use of multiple treatments that target different cell death cascades, or single agents that moderate multiple cell death pathways, is likely to lead to more effective neuroprotection for clinical disorders.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/4217920" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="66128f460c807853a85323b434b44ca0" rel="nofollow" data-download="{"attachment_id":49981946,"asset_id":4217920,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/49981946/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="5104576" href="https://independent.academia.edu/YakovlevAlexander">Alexander Yakovlev</a><script data-card-contents-for-user="5104576" type="text/json">{"id":5104576,"first_name":"Alexander","last_name":"Yakovlev","domain_name":"independent","page_name":"YakovlevAlexander","display_name":"Alexander Yakovlev","profile_url":"https://independent.academia.edu/YakovlevAlexander?f_ri=24731","photo":"https://0.academia-photos.com/5104576/2234024/2614131/s65_alexander.yakovlev.jpg"}</script></span></span></li><li class="js-paper-rank-work_4217920 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="4217920"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 4217920, container: ".js-paper-rank-work_4217920", }); });</script></li><li class="js-percentile-work_4217920 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 4217920; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_4217920"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_4217920 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="4217920"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 4217920; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=4217920]").text(description); $(".js-view-count-work_4217920").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_4217920").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="4217920"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">10</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="35637" rel="nofollow" href="https://www.academia.edu/Documents/in/Molecular_Mechanics">Molecular Mechanics</a>, <script data-card-contents-for-ri="35637" type="text/json">{"id":35637,"name":"Molecular Mechanics","url":"https://www.academia.edu/Documents/in/Molecular_Mechanics?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="38139" rel="nofollow" href="https://www.academia.edu/Documents/in/Protein_synthesis">Protein synthesis</a>, <script data-card-contents-for-ri="38139" type="text/json">{"id":38139,"name":"Protein synthesis","url":"https://www.academia.edu/Documents/in/Protein_synthesis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="61474" rel="nofollow" href="https://www.academia.edu/Documents/in/Brain">Brain</a><script data-card-contents-for-ri="61474" type="text/json">{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=4217920]'), work: {"id":4217920,"title":"Mechanisms of neural cell death: Implications for development of neuroprotective treatment strategies","created_at":"2013-08-11T12:38:46.115-07:00","url":"https://www.academia.edu/4217920/Mechanisms_of_neural_cell_death_Implications_for_development_of_neuroprotective_treatment_strategies?f_ri=24731","dom_id":"work_4217920","summary":"It has been increasingly recognized that cell death phenotypes and their molecular mechanisms are highly diverse. Necrosis is no longer considered a single entity, passively mediated by energy failure. Moreover, caspase-dependent apoptosis is not the only pathway involved in programmed cell death or even the only apoptotic mechanism. Recent experimental work emphasizes the diverse and interrelated nature of cell death mechanisms. Thus, there are both caspase-dependent and caspase-independent forms of apoptosis, which may differ morphologically as well as mechanistically. There are also necrotic-like phenotypes that requirede novo protein synthesis and are, therefore, forms of programmed cell death. In addition, forms of cell death showing certain morphological features of both necrosis and apoptosis have been identified, leading to the term aponecrosis. Considerable experimental evidence also shows that modulation of one form of cell death may lead to another. Together, these observations underscore the need to substantially revise our conceptions about neuroprotection strategies. Use of multiple treatments that target different cell death cascades, or single agents that moderate multiple cell death pathways, is likely to lead to more effective neuroprotection for clinical disorders.","downloadable_attachments":[{"id":49981946,"asset_id":4217920,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":5104576,"first_name":"Alexander","last_name":"Yakovlev","domain_name":"independent","page_name":"YakovlevAlexander","display_name":"Alexander Yakovlev","profile_url":"https://independent.academia.edu/YakovlevAlexander?f_ri=24731","photo":"https://0.academia-photos.com/5104576/2234024/2614131/s65_alexander.yakovlev.jpg"}],"research_interests":[{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":35637,"name":"Molecular Mechanics","url":"https://www.academia.edu/Documents/in/Molecular_Mechanics?f_ri=24731","nofollow":true},{"id":38139,"name":"Protein synthesis","url":"https://www.academia.edu/Documents/in/Protein_synthesis?f_ri=24731","nofollow":true},{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain?f_ri=24731","nofollow":true},{"id":112576,"name":"Cell Death","url":"https://www.academia.edu/Documents/in/Cell_Death?f_ri=24731"},{"id":175490,"name":"Programmed cell death","url":"https://www.academia.edu/Documents/in/Programmed_cell_death?f_ri=24731"},{"id":193974,"name":"Neurons","url":"https://www.academia.edu/Documents/in/Neurons?f_ri=24731"},{"id":247477,"name":"Caspase","url":"https://www.academia.edu/Documents/in/Caspase?f_ri=24731"},{"id":323406,"name":"Calpain","url":"https://www.academia.edu/Documents/in/Calpain?f_ri=24731"},{"id":1953419,"name":"Neuroprotective Agents","url":"https://www.academia.edu/Documents/in/Neuroprotective_Agents?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_4533963" data-work_id="4533963" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/4533963/Epigallocatechin_3Gallate_suppresses_early_stage_but_not_late_stage_prostate_cancer_in_TRAMP_mice_Mechanisms_of_action">Epigallocatechin-3Gallate suppresses early stage, but not late stage prostate cancer in TRAMP mice: Mechanisms of action</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">BACKGROUNDProstate cancer (PCa) is the second leading cause of cancer-related death in men in the United States. Many men have implemented purported chemopreventive agents into their daily diet in an attempt to delay the early onset of a... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_4533963" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">BACKGROUNDProstate cancer (PCa) is the second leading cause of cancer-related death in men in the United States. Many men have implemented purported chemopreventive agents into their daily diet in an attempt to delay the early onset of a PCa. Green tea polyphenols, one such agent, has been shown to be chemopreventive in skin, breast, and prostate cancers. We hypothesized that Epigallocatechin-3-Gallate (EGCG), the major polyphenol found in green tea, will exert its chemopreventive effect in the prostate via regulation of sex steroid receptor, growth factor-signaling, and inflammatory pathways.Prostate cancer (PCa) is the second leading cause of cancer-related death in men in the United States. Many men have implemented purported chemopreventive agents into their daily diet in an attempt to delay the early onset of a PCa. Green tea polyphenols, one such agent, has been shown to be chemopreventive in skin, breast, and prostate cancers. We hypothesized that Epigallocatechin-3-Gallate (EGCG), the major polyphenol found in green tea, will exert its chemopreventive effect in the prostate via regulation of sex steroid receptor, growth factor-signaling, and inflammatory pathways.METHODSFive-week-old male TRAMP (Transgenic Adenocarcinoma Mouse Prostate) offspring were fed AIN-76A diet and 0.06% EGCG in tap water. Animals were sacrificed at 28 weeks of age and the entire prostates were scored histopathologically. In addition, animals were sacrificed at 12 weeks of age and ventral (VP) and dorsolateral (DLP) prostates were removed for histopathological evaluation and immunoblot analyses or ELISA.Five-week-old male TRAMP (Transgenic Adenocarcinoma Mouse Prostate) offspring were fed AIN-76A diet and 0.06% EGCG in tap water. Animals were sacrificed at 28 weeks of age and the entire prostates were scored histopathologically. In addition, animals were sacrificed at 12 weeks of age and ventral (VP) and dorsolateral (DLP) prostates were removed for histopathological evaluation and immunoblot analyses or ELISA.RESULTSEGCG, inhibited early but not late stage PCa in the current study. In the VP, EGCG significantly reduced cell proliferation, induced apoptosis, and decreased androgen receptor (AR), insulin-like growth factor-1 (IGF-1), IGF-1 receptor (IGF-1R), phospho-extracellular signal-regulated kinases 1 and 2 (phospho-ERKs 1 and 2), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS).EGCG, inhibited early but not late stage PCa in the current study. In the VP, EGCG significantly reduced cell proliferation, induced apoptosis, and decreased androgen receptor (AR), insulin-like growth factor-1 (IGF-1), IGF-1 receptor (IGF-1R), phospho-extracellular signal-regulated kinases 1 and 2 (phospho-ERKs 1 and 2), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS).CONCLUSIONSThe attenuation of the AR, the down-regulation of potent growth factor IGF-1, modulation of inflammation biomarkers, and decrease in the MAPK signaling may contribute to the reduction in cell proliferation and induction of apoptosis and hence provide a biochemical basis for EGCG suppressing PCa without toxicity. Prostate 67: 1576–1589, 2007. © 2007 Wiley-Liss, Inc.The attenuation of the AR, the down-regulation of potent growth factor IGF-1, modulation of inflammation biomarkers, and decrease in the MAPK signaling may contribute to the reduction in cell proliferation and induction of apoptosis and hence provide a biochemical basis for EGCG suppressing PCa without toxicity. Prostate 67: 1576–1589, 2007. © 2007 Wiley-Liss, Inc.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/4533963" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="0b746b4a7f7ee00043c2a20ecdac4adc" rel="nofollow" data-download="{"attachment_id":49801433,"asset_id":4533963,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/49801433/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="5649423" href="https://independent.academia.edu/BrijeshPatel8">Brijesh Patel</a><script data-card-contents-for-user="5649423" type="text/json">{"id":5649423,"first_name":"Brijesh","last_name":"Patel","domain_name":"independent","page_name":"BrijeshPatel8","display_name":"Brijesh Patel","profile_url":"https://independent.academia.edu/BrijeshPatel8?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_4533963 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="4533963"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 4533963, container: ".js-paper-rank-work_4533963", }); });</script></li><li class="js-percentile-work_4533963 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 4533963; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_4533963"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_4533963 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="4533963"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 4533963; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=4533963]").text(description); $(".js-view-count-work_4533963").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_4533963").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="4533963"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">11</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="8914" rel="nofollow" href="https://www.academia.edu/Documents/in/Protein_Science">Protein Science</a>, <script data-card-contents-for-ri="8914" type="text/json">{"id":8914,"name":"Protein Science","url":"https://www.academia.edu/Documents/in/Protein_Science?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="12980" rel="nofollow" href="https://www.academia.edu/Documents/in/Prostate_Cancer">Prostate Cancer</a>, <script data-card-contents-for-ri="12980" type="text/json">{"id":12980,"name":"Prostate Cancer","url":"https://www.academia.edu/Documents/in/Prostate_Cancer?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="84760" rel="nofollow" href="https://www.academia.edu/Documents/in/Mice">Mice</a><script data-card-contents-for-ri="84760" type="text/json">{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=4533963]'), work: {"id":4533963,"title":"Epigallocatechin-3Gallate suppresses early stage, but not late stage prostate cancer in TRAMP mice: Mechanisms of action","created_at":"2013-09-19T20:07:30.159-07:00","url":"https://www.academia.edu/4533963/Epigallocatechin_3Gallate_suppresses_early_stage_but_not_late_stage_prostate_cancer_in_TRAMP_mice_Mechanisms_of_action?f_ri=24731","dom_id":"work_4533963","summary":"BACKGROUNDProstate cancer (PCa) is the second leading cause of cancer-related death in men in the United States. Many men have implemented purported chemopreventive agents into their daily diet in an attempt to delay the early onset of a PCa. Green tea polyphenols, one such agent, has been shown to be chemopreventive in skin, breast, and prostate cancers. We hypothesized that Epigallocatechin-3-Gallate (EGCG), the major polyphenol found in green tea, will exert its chemopreventive effect in the prostate via regulation of sex steroid receptor, growth factor-signaling, and inflammatory pathways.Prostate cancer (PCa) is the second leading cause of cancer-related death in men in the United States. Many men have implemented purported chemopreventive agents into their daily diet in an attempt to delay the early onset of a PCa. Green tea polyphenols, one such agent, has been shown to be chemopreventive in skin, breast, and prostate cancers. We hypothesized that Epigallocatechin-3-Gallate (EGCG), the major polyphenol found in green tea, will exert its chemopreventive effect in the prostate via regulation of sex steroid receptor, growth factor-signaling, and inflammatory pathways.METHODSFive-week-old male TRAMP (Transgenic Adenocarcinoma Mouse Prostate) offspring were fed AIN-76A diet and 0.06% EGCG in tap water. Animals were sacrificed at 28 weeks of age and the entire prostates were scored histopathologically. In addition, animals were sacrificed at 12 weeks of age and ventral (VP) and dorsolateral (DLP) prostates were removed for histopathological evaluation and immunoblot analyses or ELISA.Five-week-old male TRAMP (Transgenic Adenocarcinoma Mouse Prostate) offspring were fed AIN-76A diet and 0.06% EGCG in tap water. Animals were sacrificed at 28 weeks of age and the entire prostates were scored histopathologically. In addition, animals were sacrificed at 12 weeks of age and ventral (VP) and dorsolateral (DLP) prostates were removed for histopathological evaluation and immunoblot analyses or ELISA.RESULTSEGCG, inhibited early but not late stage PCa in the current study. In the VP, EGCG significantly reduced cell proliferation, induced apoptosis, and decreased androgen receptor (AR), insulin-like growth factor-1 (IGF-1), IGF-1 receptor (IGF-1R), phospho-extracellular signal-regulated kinases 1 and 2 (phospho-ERKs 1 and 2), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS).EGCG, inhibited early but not late stage PCa in the current study. In the VP, EGCG significantly reduced cell proliferation, induced apoptosis, and decreased androgen receptor (AR), insulin-like growth factor-1 (IGF-1), IGF-1 receptor (IGF-1R), phospho-extracellular signal-regulated kinases 1 and 2 (phospho-ERKs 1 and 2), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS).CONCLUSIONSThe attenuation of the AR, the down-regulation of potent growth factor IGF-1, modulation of inflammation biomarkers, and decrease in the MAPK signaling may contribute to the reduction in cell proliferation and induction of apoptosis and hence provide a biochemical basis for EGCG suppressing PCa without toxicity. Prostate 67: 1576–1589, 2007. © 2007 Wiley-Liss, Inc.The attenuation of the AR, the down-regulation of potent growth factor IGF-1, modulation of inflammation biomarkers, and decrease in the MAPK signaling may contribute to the reduction in cell proliferation and induction of apoptosis and hence provide a biochemical basis for EGCG suppressing PCa without toxicity. Prostate 67: 1576–1589, 2007. © 2007 Wiley-Liss, Inc.","downloadable_attachments":[{"id":49801433,"asset_id":4533963,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":5649423,"first_name":"Brijesh","last_name":"Patel","domain_name":"independent","page_name":"BrijeshPatel8","display_name":"Brijesh Patel","profile_url":"https://independent.academia.edu/BrijeshPatel8?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":8914,"name":"Protein Science","url":"https://www.academia.edu/Documents/in/Protein_Science?f_ri=24731","nofollow":true},{"id":12980,"name":"Prostate Cancer","url":"https://www.academia.edu/Documents/in/Prostate_Cancer?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice?f_ri=24731","nofollow":true},{"id":161176,"name":"The","url":"https://www.academia.edu/Documents/in/The?f_ri=24731"},{"id":161553,"name":"Prostate","url":"https://www.academia.edu/Documents/in/Prostate?f_ri=24731"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731"},{"id":725615,"name":"Mechanism of action","url":"https://www.academia.edu/Documents/in/Mechanism_of_action?f_ri=24731"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation?f_ri=24731"},{"id":1223957,"name":"Catechin","url":"https://www.academia.edu/Documents/in/Catechin?f_ri=24731"},{"id":1745478,"name":"Adenocarcinoma","url":"https://www.academia.edu/Documents/in/Adenocarcinoma?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_4560905" data-work_id="4560905" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/4560905/Relationship_of_total_serum_sialic_acid_to_sialylglycoprotein_acute_phase_reactants_in_malignant_melanoma">Relationship of total serum sialic acid to sialylglycoprotein acute-phase reactants in malignant melanoma</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Reported elevations of total serum sialic acid may be a result of shed tumour-related membrane sialylglycoprotein and/or concurrent elevation of nonspecific, acute-phase reactant sialylglycoprotein. To clarify further the specificity and... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_4560905" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Reported elevations of total serum sialic acid may be a result of shed tumour-related membrane sialylglycoprotein and/or concurrent elevation of nonspecific, acute-phase reactant sialylglycoprotein. To clarify further the specificity and sensitivity of serum sialic acid monitoring, analyses of sialic acid by the thiobarbituric acid method and acute-phase reactants by radial immunodiffusion were made using the same malignant melanoma patients' sera. Preliminary studies of IgG, IgA, IgM, ceruloplasmin and C-reactive protein suggested that these would not be valuable monitors of tumour burden. Single serum samples from 59 melanoma patients and age-and sex-matched controls were further examined for sialic acid, a -acid glycoprotein, a -antitrypsin, haptoglobin, and a2-macroglobulin. Patients were grouped according to tumour burden. In pairwise statistical tests, differences between groups tended to be greater for sialic acid than for acute-phase reactants. On discriminant analysis, sialic acid was clearly the most significant single discriminator between groups, with an F statistic of P < 0-00005. Although a, -acid glycoprotein was quite strongly correlated with sialic acid, it was not such a good discriminator and did not add significantly to the predictive power of sialic acid alone.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/4560905" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="05f3b9126735aec3ae6b604a89544bfd" rel="nofollow" data-download="{"attachment_id":49789694,"asset_id":4560905,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/49789694/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="5704238" href="https://epn.academia.edu/FernandoSalinas">Fernando Salinas</a><script data-card-contents-for-user="5704238" type="text/json">{"id":5704238,"first_name":"Fernando","last_name":"Salinas","domain_name":"epn","page_name":"FernandoSalinas","display_name":"Fernando Salinas","profile_url":"https://epn.academia.edu/FernandoSalinas?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_4560905 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="4560905"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 4560905, container: ".js-paper-rank-work_4560905", }); 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$(".js-view-count[data-work-id=4560905]").text(description); $(".js-view-count-work_4560905").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_4560905").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="4560905"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">14</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="33319" rel="nofollow" href="https://www.academia.edu/Documents/in/Nature">Nature</a>, <script data-card-contents-for-ri="33319" type="text/json">{"id":33319,"name":"Nature","url":"https://www.academia.edu/Documents/in/Nature?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="38650" rel="nofollow" href="https://www.academia.edu/Documents/in/Cell_Division">Cell Division</a>, <script data-card-contents-for-ri="38650" type="text/json">{"id":38650,"name":"Cell Division","url":"https://www.academia.edu/Documents/in/Cell_Division?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="52489" rel="nofollow" href="https://www.academia.edu/Documents/in/Adipose_tissue">Adipose tissue</a><script data-card-contents-for-ri="52489" type="text/json">{"id":52489,"name":"Adipose tissue","url":"https://www.academia.edu/Documents/in/Adipose_tissue?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=4560905]'), work: {"id":4560905,"title":"Relationship of total serum sialic acid to sialylglycoprotein acute-phase reactants in malignant melanoma","created_at":"2013-09-23T03:07:32.596-07:00","url":"https://www.academia.edu/4560905/Relationship_of_total_serum_sialic_acid_to_sialylglycoprotein_acute_phase_reactants_in_malignant_melanoma?f_ri=24731","dom_id":"work_4560905","summary":"Reported elevations of total serum sialic acid may be a result of shed tumour-related membrane sialylglycoprotein and/or concurrent elevation of nonspecific, acute-phase reactant sialylglycoprotein. To clarify further the specificity and sensitivity of serum sialic acid monitoring, analyses of sialic acid by the thiobarbituric acid method and acute-phase reactants by radial immunodiffusion were made using the same malignant melanoma patients' sera. Preliminary studies of IgG, IgA, IgM, ceruloplasmin and C-reactive protein suggested that these would not be valuable monitors of tumour burden. Single serum samples from 59 melanoma patients and age-and sex-matched controls were further examined for sialic acid, a -acid glycoprotein, a -antitrypsin, haptoglobin, and a2-macroglobulin. Patients were grouped according to tumour burden. In pairwise statistical tests, differences between groups tended to be greater for sialic acid than for acute-phase reactants. On discriminant analysis, sialic acid was clearly the most significant single discriminator between groups, with an F statistic of P \u003c 0-00005. Although a, -acid glycoprotein was quite strongly correlated with sialic acid, it was not such a good discriminator and did not add significantly to the predictive power of sialic acid alone.","downloadable_attachments":[{"id":49789694,"asset_id":4560905,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":5704238,"first_name":"Fernando","last_name":"Salinas","domain_name":"epn","page_name":"FernandoSalinas","display_name":"Fernando Salinas","profile_url":"https://epn.academia.edu/FernandoSalinas?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":33319,"name":"Nature","url":"https://www.academia.edu/Documents/in/Nature?f_ri=24731","nofollow":true},{"id":38650,"name":"Cell Division","url":"https://www.academia.edu/Documents/in/Cell_Division?f_ri=24731","nofollow":true},{"id":52489,"name":"Adipose tissue","url":"https://www.academia.edu/Documents/in/Adipose_tissue?f_ri=24731","nofollow":true},{"id":63360,"name":"Discriminant Analysis","url":"https://www.academia.edu/Documents/in/Discriminant_Analysis?f_ri=24731"},{"id":99023,"name":"Melanoma","url":"https://www.academia.edu/Documents/in/Melanoma?f_ri=24731"},{"id":295452,"name":"C reactive protein","url":"https://www.academia.edu/Documents/in/C_reactive_protein?f_ri=24731"},{"id":383086,"name":"Ceruloplasmin","url":"https://www.academia.edu/Documents/in/Ceruloplasmin?f_ri=24731"},{"id":553283,"name":"Cancer cells","url":"https://www.academia.edu/Documents/in/Cancer_cells?f_ri=24731"},{"id":703835,"name":"Statistical Test","url":"https://www.academia.edu/Documents/in/Statistical_Test?f_ri=24731"},{"id":1010893,"name":"Cancers","url":"https://www.academia.edu/Documents/in/Cancers?f_ri=24731"},{"id":1312086,"name":"Immunoglobulins","url":"https://www.academia.edu/Documents/in/Immunoglobulins?f_ri=24731"},{"id":1654599,"name":"Alpha-1 Antitrypsin","url":"https://www.academia.edu/Documents/in/Alpha-1_Antitrypsin?f_ri=24731"},{"id":1743783,"name":"Sialic Acids","url":"https://www.academia.edu/Documents/in/Sialic_Acids?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_5622718" data-work_id="5622718" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/5622718/Direct_Evidence_for_the_Contribution_of_Activated_N_ras_and_K_ras_Oncogenes_to_Increased_Intrinsic_Radiation_Resistance_in_Human_Tumor_Cell_Lines1">Direct Evidence for the Contribution of Activated N-ras and K-ras Oncogenes to Increased Intrinsic Radiation Resistance in Human Tumor Cell Lines1</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Transformation with ras oncogenes results in increased radiation survival in many but not all cells. In addition, prenyltransferase inhibitors, which inhibit ras proteins by blocking posttranslational modification, radiosensitize cells... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_5622718" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Transformation with ras oncogenes results in increased radiation survival in many but not all cells. In addition, prenyltransferase inhibitors, which inhibit ras proteins by blocking posttranslational modification, radiosensitize cells with oncogenic ras. These findings suggest that oncogenic ras contributes to intrinsic radiation resistance.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/5622718" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="4206bebbb825e22479bf740150207b5e" rel="nofollow" data-download="{"attachment_id":32693917,"asset_id":5622718,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/32693917/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="8062076" href="https://independent.academia.edu/SwatiGupta26">Swati Gupta</a><script data-card-contents-for-user="8062076" type="text/json">{"id":8062076,"first_name":"Swati","last_name":"Gupta","domain_name":"independent","page_name":"SwatiGupta26","display_name":"Swati Gupta","profile_url":"https://independent.academia.edu/SwatiGupta26?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_5622718 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="5622718"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 5622718, container: ".js-paper-rank-work_5622718", }); });</script></li><li class="js-percentile-work_5622718 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 5622718; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_5622718"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_5622718 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="5622718"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 5622718; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=5622718]").text(description); $(".js-view-count-work_5622718").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_5622718").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="5622718"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">9</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="156" rel="nofollow" href="https://www.academia.edu/Documents/in/Genetics">Genetics</a>, <script data-card-contents-for-ri="156" type="text/json">{"id":156,"name":"Genetics","url":"https://www.academia.edu/Documents/in/Genetics?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="6021" rel="nofollow" href="https://www.academia.edu/Documents/in/Cancer">Cancer</a>, <script data-card-contents-for-ri="6021" type="text/json">{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a>, <script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="38650" rel="nofollow" href="https://www.academia.edu/Documents/in/Cell_Division">Cell Division</a><script data-card-contents-for-ri="38650" type="text/json">{"id":38650,"name":"Cell Division","url":"https://www.academia.edu/Documents/in/Cell_Division?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=5622718]'), work: {"id":5622718,"title":"Direct Evidence for the Contribution of Activated N-ras and K-ras Oncogenes to Increased Intrinsic Radiation Resistance in Human Tumor Cell Lines1","created_at":"2014-01-06T12:34:12.251-08:00","url":"https://www.academia.edu/5622718/Direct_Evidence_for_the_Contribution_of_Activated_N_ras_and_K_ras_Oncogenes_to_Increased_Intrinsic_Radiation_Resistance_in_Human_Tumor_Cell_Lines1?f_ri=24731","dom_id":"work_5622718","summary":"Transformation with ras oncogenes results in increased radiation survival in many but not all cells. In addition, prenyltransferase inhibitors, which inhibit ras proteins by blocking posttranslational modification, radiosensitize cells with oncogenic ras. These findings suggest that oncogenic ras contributes to intrinsic radiation resistance.","downloadable_attachments":[{"id":32693917,"asset_id":5622718,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":8062076,"first_name":"Swati","last_name":"Gupta","domain_name":"independent","page_name":"SwatiGupta26","display_name":"Swati Gupta","profile_url":"https://independent.academia.edu/SwatiGupta26?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":156,"name":"Genetics","url":"https://www.academia.edu/Documents/in/Genetics?f_ri=24731","nofollow":true},{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":38650,"name":"Cell Division","url":"https://www.academia.edu/Documents/in/Cell_Division?f_ri=24731","nofollow":true},{"id":176901,"name":"Fibrosarcoma","url":"https://www.academia.edu/Documents/in/Fibrosarcoma?f_ri=24731"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival?f_ri=24731"},{"id":1159983,"name":"Radiation Tolerance","url":"https://www.academia.edu/Documents/in/Radiation_Tolerance?f_ri=24731"},{"id":1745478,"name":"Adenocarcinoma","url":"https://www.academia.edu/Documents/in/Adenocarcinoma?f_ri=24731"},{"id":2440562,"name":"Colorectal Neoplasms","url":"https://www.academia.edu/Documents/in/Colorectal_Neoplasms?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_6172693" data-work_id="6172693" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/6172693/Gene_expression_in_women_conceiving_spontaneously_over_the_age_of_45_years">Gene expression in women conceiving spontaneously over the age of 45 years</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Objective: To examine gene expression profiles of women conceiving spontaneously after the age of 45. Design: Expression profiling by complementary DNA microarray analysis. Setting: University departments. Patient(s): Eight women 45 years... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_6172693" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Objective: To examine gene expression profiles of women conceiving spontaneously after the age of 45. Design: Expression profiling by complementary DNA microarray analysis. Setting: University departments. Patient(s): Eight women 45 years or older (study group) who conceived spontaneously and were 6 months after their last delivery were compared with six women aged 45 years old (control group) who had their last delivery before the age of 30. Intervention(s): Blood samples were collected from each woman for RNA isolation from peripheral blood mononuclear cells (PBMC). Main Outcome Measure(s): Expression profiles of PBMC isolated from each woman were determined by using Affymetrix DNA microarray analysis covering about 15,000 identified genes. Result(s): Microarray of global gene expression revealed 671 genes that showed statistically significant differential expression between the study and control groups: 383 genes were overexpressed and 288 were underexpressed. The most significant functional groups defining these genes were: apoptosis, ubiquitination, and energy production. As many as 60 genes also participated in ovarian physiology. Conclusion(s): These observations suggest that extended fertility is associated with a unique ability to enrich cellular processes, leading to delayed ovarian senescence. (Fertil Steril Ò 2008;-:---.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/6172693" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="d66a0a0d2eb87583fbb875cf3a3d328a" rel="nofollow" data-download="{"attachment_id":48984827,"asset_id":6172693,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/48984827/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="9399388" href="https://independent.academia.edu/YoelBogoch">Yoel Bogoch</a><script data-card-contents-for-user="9399388" type="text/json">{"id":9399388,"first_name":"Yoel","last_name":"Bogoch","domain_name":"independent","page_name":"YoelBogoch","display_name":"Yoel Bogoch","profile_url":"https://independent.academia.edu/YoelBogoch?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_6172693 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="6172693"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 6172693, container: ".js-paper-rank-work_6172693", }); });</script></li><li class="js-percentile-work_6172693 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 6172693; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_6172693"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_6172693 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="6172693"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 6172693; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=6172693]").text(description); $(".js-view-count-work_6172693").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_6172693").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="6172693"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">16</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="3701" rel="nofollow" href="https://www.academia.edu/Documents/in/RNA">RNA</a>, <script data-card-contents-for-ri="3701" type="text/json">{"id":3701,"name":"RNA","url":"https://www.academia.edu/Documents/in/RNA?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="6791" rel="nofollow" href="https://www.academia.edu/Documents/in/Aging">Aging</a>, <script data-card-contents-for-ri="6791" type="text/json">{"id":6791,"name":"Aging","url":"https://www.academia.edu/Documents/in/Aging?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="8954" rel="nofollow" href="https://www.academia.edu/Documents/in/Fertility">Fertility</a>, <script data-card-contents-for-ri="8954" type="text/json">{"id":8954,"name":"Fertility","url":"https://www.academia.edu/Documents/in/Fertility?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a><script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=6172693]'), work: {"id":6172693,"title":"Gene expression in women conceiving spontaneously over the age of 45 years","created_at":"2014-02-22T14:43:26.028-08:00","url":"https://www.academia.edu/6172693/Gene_expression_in_women_conceiving_spontaneously_over_the_age_of_45_years?f_ri=24731","dom_id":"work_6172693","summary":"Objective: To examine gene expression profiles of women conceiving spontaneously after the age of 45. Design: Expression profiling by complementary DNA microarray analysis. Setting: University departments. Patient(s): Eight women 45 years or older (study group) who conceived spontaneously and were 6 months after their last delivery were compared with six women aged 45 years old (control group) who had their last delivery before the age of 30. Intervention(s): Blood samples were collected from each woman for RNA isolation from peripheral blood mononuclear cells (PBMC). Main Outcome Measure(s): Expression profiles of PBMC isolated from each woman were determined by using Affymetrix DNA microarray analysis covering about 15,000 identified genes. Result(s): Microarray of global gene expression revealed 671 genes that showed statistically significant differential expression between the study and control groups: 383 genes were overexpressed and 288 were underexpressed. The most significant functional groups defining these genes were: apoptosis, ubiquitination, and energy production. As many as 60 genes also participated in ovarian physiology. Conclusion(s): These observations suggest that extended fertility is associated with a unique ability to enrich cellular processes, leading to delayed ovarian senescence. (Fertil Steril Ò 2008;-:---.","downloadable_attachments":[{"id":48984827,"asset_id":6172693,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":9399388,"first_name":"Yoel","last_name":"Bogoch","domain_name":"independent","page_name":"YoelBogoch","display_name":"Yoel Bogoch","profile_url":"https://independent.academia.edu/YoelBogoch?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":3701,"name":"RNA","url":"https://www.academia.edu/Documents/in/RNA?f_ri=24731","nofollow":true},{"id":6791,"name":"Aging","url":"https://www.academia.edu/Documents/in/Aging?f_ri=24731","nofollow":true},{"id":8954,"name":"Fertility","url":"https://www.academia.edu/Documents/in/Fertility?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":27784,"name":"Gene expression","url":"https://www.academia.edu/Documents/in/Gene_expression?f_ri=24731"},{"id":36213,"name":"Energy Metabolism","url":"https://www.academia.edu/Documents/in/Energy_Metabolism?f_ri=24731"},{"id":55266,"name":"Ubiquitin","url":"https://www.academia.edu/Documents/in/Ubiquitin?f_ri=24731"},{"id":62550,"name":"Pregnancy","url":"https://www.academia.edu/Documents/in/Pregnancy?f_ri=24731"},{"id":98922,"name":"Fertility and Sterility","url":"https://www.academia.edu/Documents/in/Fertility_and_Sterility?f_ri=24731"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences?f_ri=24731"},{"id":402446,"name":"Maternal Age","url":"https://www.academia.edu/Documents/in/Maternal_Age?f_ri=24731"},{"id":410370,"name":"Public health systems and services research","url":"https://www.academia.edu/Documents/in/Public_health_systems_and_services_research-1?f_ri=24731"},{"id":869175,"name":"Ovary","url":"https://www.academia.edu/Documents/in/Ovary?f_ri=24731"},{"id":1200339,"name":"Female Fertility","url":"https://www.academia.edu/Documents/in/Female_Fertility?f_ri=24731"},{"id":1763968,"name":"Gene Expression Regulation","url":"https://www.academia.edu/Documents/in/Gene_Expression_Regulation?f_ri=24731"},{"id":1810445,"name":"Gene expression profiling","url":"https://www.academia.edu/Documents/in/Gene_expression_profiling?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_28271667" data-work_id="28271667" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/28271667/Growth_hormone_as_a_neuronal_rescue_factor_during_recovery_from_CNS_injury">Growth hormone as a neuronal rescue factor during recovery from CNS injury</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">AbstractöThere is growing evidence to suggest that growth hormone plays a role in the growth and development of the CNS. Speci¢cally, growth hormone has been implicated in promoting brain growth, myelination, neuronal arborisation, glial... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_28271667" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">AbstractöThere is growing evidence to suggest that growth hormone plays a role in the growth and development of the CNS. Speci¢cally, growth hormone has been implicated in promoting brain growth, myelination, neuronal arborisation, glial di¡erentiation and cognitive function. Here we investigate if growth hormone has a role in the recovery from an unilateral hypoxic^ischaemic brain injury. Using moderate (15 min hypoxia) and severe (60 min hypoxia) models of hypoxic^ischaemia in juvenile rats and standard immunohistochemical techniques, we found intense growth hormone-like immunoreactivity present within regions of cell loss by 3 days (P 6 0.05). Growth hormone-like immunoreactivity was observed on injured neurones, myelinated axons, glial cells within and surrounding infarcted tissue and on the choroid plexus plus ependymal cells within the injured hemisphere. The pattern of immunoreactivity suggests that (a) growth hormone (or a growth hormone-like substance) is transported via the cerebrospinal £uid and (b) that growth hormone (or a growth hormone-like substance) is acting in a neurotrophic manner speci¢cally targeted to injured neurones and glia.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/28271667" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="9d571131c402aa8f63946f2533dbac6b" rel="nofollow" data-download="{"attachment_id":48596758,"asset_id":28271667,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/48596758/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="52995281" href="https://independent.academia.edu/ArjanScheepens">Arjan Scheepens</a><script data-card-contents-for-user="52995281" type="text/json">{"id":52995281,"first_name":"Arjan","last_name":"Scheepens","domain_name":"independent","page_name":"ArjanScheepens","display_name":"Arjan Scheepens","profile_url":"https://independent.academia.edu/ArjanScheepens?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_28271667 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="28271667"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 28271667, container: ".js-paper-rank-work_28271667", }); });</script></li><li class="js-percentile-work_28271667 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 28271667; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_28271667"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_28271667 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="28271667"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 28271667; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=28271667]").text(description); $(".js-view-count-work_28271667").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_28271667").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="28271667"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">23</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="161" rel="nofollow" href="https://www.academia.edu/Documents/in/Neuroscience">Neuroscience</a>, <script data-card-contents-for-ri="161" type="text/json">{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="221" rel="nofollow" href="https://www.academia.edu/Documents/in/Psychology">Psychology</a>, <script data-card-contents-for-ri="221" type="text/json">{"id":221,"name":"Psychology","url":"https://www.academia.edu/Documents/in/Psychology?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="12071" rel="nofollow" href="https://www.academia.edu/Documents/in/Immunohistochemistry">Immunohistochemistry</a>, <script data-card-contents-for-ri="12071" type="text/json">{"id":12071,"name":"Immunohistochemistry","url":"https://www.academia.edu/Documents/in/Immunohistochemistry?f_ri=24731","nofollow":true}</script><a class="InlineList-item-text" data-has-card-for-ri="24731" rel="nofollow" href="https://www.academia.edu/Documents/in/Apoptosis">Apoptosis</a><script data-card-contents-for-ri="24731" type="text/json">{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=28271667]'), work: {"id":28271667,"title":"Growth hormone as a neuronal rescue factor during recovery from CNS injury","created_at":"2016-09-05T14:57:12.173-07:00","url":"https://www.academia.edu/28271667/Growth_hormone_as_a_neuronal_rescue_factor_during_recovery_from_CNS_injury?f_ri=24731","dom_id":"work_28271667","summary":"AbstractöThere is growing evidence to suggest that growth hormone plays a role in the growth and development of the CNS. Speci¢cally, growth hormone has been implicated in promoting brain growth, myelination, neuronal arborisation, glial di¡erentiation and cognitive function. Here we investigate if growth hormone has a role in the recovery from an unilateral hypoxic^ischaemic brain injury. Using moderate (15 min hypoxia) and severe (60 min hypoxia) models of hypoxic^ischaemia in juvenile rats and standard immunohistochemical techniques, we found intense growth hormone-like immunoreactivity present within regions of cell loss by 3 days (P 6 0.05). Growth hormone-like immunoreactivity was observed on injured neurones, myelinated axons, glial cells within and surrounding infarcted tissue and on the choroid plexus plus ependymal cells within the injured hemisphere. The pattern of immunoreactivity suggests that (a) growth hormone (or a growth hormone-like substance) is transported via the cerebrospinal £uid and (b) that growth hormone (or a growth hormone-like substance) is acting in a neurotrophic manner speci¢cally targeted to injured neurones and glia.","downloadable_attachments":[{"id":48596758,"asset_id":28271667,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":52995281,"first_name":"Arjan","last_name":"Scheepens","domain_name":"independent","page_name":"ArjanScheepens","display_name":"Arjan Scheepens","profile_url":"https://independent.academia.edu/ArjanScheepens?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience?f_ri=24731","nofollow":true},{"id":221,"name":"Psychology","url":"https://www.academia.edu/Documents/in/Psychology?f_ri=24731","nofollow":true},{"id":12071,"name":"Immunohistochemistry","url":"https://www.academia.edu/Documents/in/Immunohistochemistry?f_ri=24731","nofollow":true},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis?f_ri=24731","nofollow":true},{"id":29149,"name":"Extracellular Matrix","url":"https://www.academia.edu/Documents/in/Extracellular_Matrix?f_ri=24731"},{"id":52562,"name":"Growth Hormone","url":"https://www.academia.edu/Documents/in/Growth_Hormone?f_ri=24731"},{"id":61474,"name":"Brain","url":"https://www.academia.edu/Documents/in/Brain?f_ri=24731"},{"id":193974,"name":"Neurons","url":"https://www.academia.edu/Documents/in/Neurons?f_ri=24731"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats?f_ri=24731"},{"id":417494,"name":"Rat","url":"https://www.academia.edu/Documents/in/Rat?f_ri=24731"},{"id":441653,"name":"Cognitive Function","url":"https://www.academia.edu/Documents/in/Cognitive_Function?f_ri=24731"},{"id":482211,"name":"Growth Hormone Receptor","url":"https://www.academia.edu/Documents/in/Growth_Hormone_Receptor?f_ri=24731"},{"id":564879,"name":"Wistar Rats","url":"https://www.academia.edu/Documents/in/Wistar_Rats?f_ri=24731"},{"id":881608,"name":"Bovine Serum Albumin","url":"https://www.academia.edu/Documents/in/Bovine_Serum_Albumin?f_ri=24731"},{"id":956026,"name":"Somatic Cell Count","url":"https://www.academia.edu/Documents/in/Somatic_Cell_Count?f_ri=24731"},{"id":990417,"name":"Recombinant Proteins","url":"https://www.academia.edu/Documents/in/Recombinant_Proteins?f_ri=24731"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival?f_ri=24731"},{"id":1239755,"name":"Neurosciences","url":"https://www.academia.edu/Documents/in/Neurosciences?f_ri=24731"},{"id":1426712,"name":"Immunoglobulin","url":"https://www.academia.edu/Documents/in/Immunoglobulin?f_ri=24731"},{"id":1953419,"name":"Neuroprotective Agents","url":"https://www.academia.edu/Documents/in/Neuroprotective_Agents?f_ri=24731"},{"id":2418353,"name":"Phosphate Buffer Saline","url":"https://www.academia.edu/Documents/in/Phosphate_Buffer_Saline?f_ri=24731"},{"id":2450733,"name":"Brain injuries","url":"https://www.academia.edu/Documents/in/Brain_injuries?f_ri=24731"},{"id":2474622,"name":"Recovery of Function","url":"https://www.academia.edu/Documents/in/Recovery_of_Function?f_ri=24731"}]}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_28160055" data-work_id="28160055" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/28160055/Tissue_specific_induction_of_p53_targets_in_vivo">Tissue-specific induction of p53 targets in vivo</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">The in vivo response to radiotherapy is not well understood but appears to involve the p53 tumor suppressor protein. We investigated the expression of apoptosis-inducing p53 target genes during ␥-irradiation-induced cell death in p53 ؉/؉... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_28160055" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">The in vivo response to radiotherapy is not well understood but appears to involve the p53 tumor suppressor protein. We investigated the expression of apoptosis-inducing p53 target genes during ␥-irradiation-induced cell death in p53 ؉/؉ or p53 ؊/؊ mouse tissues using in situ hybridization. Our results reveal striking tissue specificity with distinct regulation of target p53-induced genes in different cells and tissue compartments, as well as variations in dependence on p53 for basal expression. p53-dependent induction of Puma occurred in the splenic white pulp, whereas Noxa and Bid were induced in the red pulp. These patterns correlated with activation of caspase-3 in both compartments. All apoptotic targets of p53 studied here (DR5, Bid, Puma, Noxa) were induced in the jejunum and ileum, which appeared to be the tissues most sensitive to irradiation. We also observed unexpected differences in p53 target gene activation between the transverse and descending colon. Finally, in the liver where irradiation did not lead to caspase-3 activation, we primarily observed p21 WAF1 induction as the major p53-dependent target gene response. Our findings indicate that the selectivity of p53 in transactivation following DNA damage in vivo results in unique tissue and cell type specificity, which may correlate with growth arrest or variable sensitivity to ␥-irradiation.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/28160055" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="f5b2cdaa28d1e69165816247e210fa7b" rel="nofollow" data-download="{"attachment_id":48475431,"asset_id":28160055,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/48475431/download_file?st=MTczOTc5Mzg1MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="52685938" href="https://independent.academia.edu/PeiwenFei">Peiwen Fei</a><script data-card-contents-for-user="52685938" type="text/json">{"id":52685938,"first_name":"Peiwen","last_name":"Fei","domain_name":"independent","page_name":"PeiwenFei","display_name":"Peiwen Fei","profile_url":"https://independent.academia.edu/PeiwenFei?f_ri=24731","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_28160055 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="28160055"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 28160055, container: ".js-paper-rank-work_28160055", }); 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We investigated the expression of apoptosis-inducing p53 target genes during ␥-irradiation-induced cell death in p53 ؉/؉ or p53 ؊/؊ mouse tissues using in situ hybridization. Our results reveal striking tissue specificity with distinct regulation of target p53-induced genes in different cells and tissue compartments, as well as variations in dependence on p53 for basal expression. p53-dependent induction of Puma occurred in the splenic white pulp, whereas Noxa and Bid were induced in the red pulp. These patterns correlated with activation of caspase-3 in both compartments. All apoptotic targets of p53 studied here (DR5, Bid, Puma, Noxa) were induced in the jejunum and ileum, which appeared to be the tissues most sensitive to irradiation. We also observed unexpected differences in p53 target gene activation between the transverse and descending colon. Finally, in the liver where irradiation did not lead to caspase-3 activation, we primarily observed p21 WAF1 induction as the major p53-dependent target gene response. Our findings indicate that the selectivity of p53 in transactivation following DNA damage in vivo results in unique tissue and cell type specificity, which may correlate with growth arrest or variable sensitivity to ␥-irradiation.","downloadable_attachments":[{"id":48475431,"asset_id":28160055,"asset_type":"Work","always_allow_download":false}],"ordered_authors":[{"id":52685938,"first_name":"Peiwen","last_name":"Fei","domain_name":"independent","page_name":"PeiwenFei","display_name":"Peiwen Fei","profile_url":"https://independent.academia.edu/PeiwenFei?f_ri=24731","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer?f_ri=24731","nofollow":true},{"id":22998,"name":"Gamma Rays","url":"https://www.academia.edu/Documents/in/Gamma_Rays?f_ri=24731","nofollow":true},{"id":23066,"name":"DNA 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